Predictors of Mortality in CNS Tuberculosis: Clinical and Radiological Parameters

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This study aimed to identify clinical, laboratory, and neuroimaging parameters associated with mortality in CNS-TB. Methods: In this retrospective study, 15 patients diagnosed with CNS-TB between 2010 and 2023 were divided into survivors (n = 6) and non-survivors (n = 9). Demographic, clinical, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) data were analyzed. Statistical comparisons and effect size analyses (Cohen’s d, h) were performed to assess clinical significance. Results: The mortality rate was 60%. Non-survivors were significantly older (57.8 ± 22.8 vs. 29.2 ± 6.9 years; P = 0.029, d = 1.56) and had higher serum AST levels (28.9 ± 6.4 vs. 15.0 ± 2.9 U/L; P = 0.007, d = 2.14). CSF leukocyte count was also significantly elevated in non-survivors (P = 0.041, d = 0.95). Cerebral ischemia was present only in non-survivors (56% vs. 0%; P = 0.04, h = 0.98). PCR positivity in non-CSF samples (0% vs. 78%) was significantly associated with mortality (P = 0.007). Other parameters showing moderate to large effect sizes included focal neurological deficits, ventriculitis, and increased CSF opening pressure. Conclusion: Advanced age, elevated AST levels, increased CSF leukocyte count, cerebral ischemia, and extraparenchymal PCR positivity emerged as major predictors of mortality in CNS-TB. These factors may aid early risk stratification and treatment planning. Larger prospective studies are warranted to validate these findings. CNS tuberculosis mortality outcome risk factors Figures Figure 1 Figure 2 1. Introduction Tuberculosis (TB) remains a critical global health issue despite advances in diagnosis and treatment. According to the World Health Organization's 2022 Global Tuberculosis Report, an estimated 10.6 million people were diagnosed with TB in 2021, and approximately 1.3 million died, underscoring the disease’s persistent threat, particularly in resource-limited settings and among immunocompromised individuals such as those with HIV infection [ 1 ]. While pulmonary TB is the most common form, extrapulmonary tuberculosis (EPTB) accounts for nearly one-third of all TB cases, and among these, central nervous system tuberculosis (CNS-TB) represents the most severe and life-threatening manifestation, comprising approximately 5–10% of EPTB cases [ 2 ]. The CNS can be affected by tuberculous meningitis, tuberculomas, abscesses, encephalitis, or spinal involvement, each carrying substantial risk for disability and death. Mortality rates in CNS-TB remain high, ranging from 15–60% in published cohorts, depending on factors such as age, immune status, comorbidities, and access to early diagnosis and appropriate therapy [ 3 , 4 ]. In Turkey, CNS-TB is rare but still seen in tertiary centers, particularly among populations with socioeconomic challenges or latent TB reactivation. The diagnosis of CNS-TB is challenging due to the nonspecific nature of early symptoms and the limited sensitivity of conventional diagnostic methods such as CSF microscopy and culture. While CSF culture remains the gold standard, its low positivity rate and prolonged turnaround time necessitate reliance on radiological findings and empirical clinical judgment in many cases [ 5 ]. Delays in diagnosis often result in patients presenting in advanced disease stages, where complications like hydrocephalus, infarction, and altered consciousness are common. To assist clinicians in evaluating disease severity and prognosis, several staging and scoring systems have been developed. The British Medical Research Council (BMRC) grading classifies CNS-TB severity based on consciousness and focal deficits, and more recent models incorporate Glasgow Coma Scale (GCS), CSF parameters, and comorbid conditions [ 6 ]. Nevertheless, there is still a lack of consensus on reliable predictors of mortality, especially when considering combined clinical, laboratory, and neuroimaging findings. This study aimed to determine the prognostic significance of specific clinical, laboratory, and neuroimaging parameters—such as age, liver enzyme levels, CSF indices, and MRI abnormalities—in relation to mortality in CNS-TB. By comparing survivors and non-survivors, we sought to identify early predictors that could inform intervetion strategies. 2. Materials andMethods This retrospective observational study included 15 patients diagnosed with central nervous system tuberculosis (CNS-TB) who were followed between January 2010 and January 2023 in the neurology and infectious diseases departments of a tertiary university hospital. Diagnosis was made based on the criteria proposed by Marais et al. [ 6 ] and national guidelines [ 7 ], including at least two of the following: typical clinical features (e.g., headache, fever, altered consciousness), CSF findings suggestive of TB (high protein, low glucose, pleocytosis), positive neuroimaging, or microbiological confirmation (culture or PCR).Patient data were retrospectively reviewed from electronic hospital records. A structured data collection form was used to extract information including demographic characteristics, presenting symptoms, neurological examination findings, CSF biochemistry, neuroimaging results, and treatment details. Based on clinical outcomes, patients were categorized into two groups: survivors (n = 6) and non-survivors (n = 9). CSF parameters analyzed included leukocyte count, protein, glucose, chloride levels, and opening pressure. Additional laboratory results such as CSF culture, PCR, and antibiogram sensitivity were also recorded. MRI findings such as meningeal contrast enhancement, hydrocephalus, tuberculoma, ventriculitis, cerebral ischemia, and cranial nerve involvement were evaluated for all patients. All patients received standardized antituberculosis therapy consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol, initiated immediately after diagnosis. Intravenous corticosteroid therapy (dexamethasone) was administered in patients with significant meningeal involvement or clinical indications. Neurosurgical interventions, such as ventriculoperitoneal shunt placement, were performed when necessary based on clinical and radiological indications. This study was approved by the Ethics Committee of Ege University Faculty of Medicine. 3. Statistical Analysis Statistical analyses were conducted using SPSS software version 26.0 (IBM Corp., Armonk, NY, USA). The distribution of continuous variables was assessed using the Shapiro–Wilk test. Normally distributed data were expressed as mean ± standard deviation, while non-normally distributed variables were reported as median with minimum and maximum values. Categorical variables were summarized as frequencies and percentages. For comparisons between survivor and non-survivor groups, independent samples t-tests were used for normally distributed continuous variables, and the Mann–Whitney U test was applied for non-normally distributed data. Categorical variables were compared using Pearson’s chi-square test or Fisher’s exact test, depending on expected cell counts. To assess the magnitude of group differences beyond statistical significance, effect size analyses were performed using Cohen’s d for continuous variables and Cohen’s h for proportions. Effect sizes were interpreted as small (0.20), medium (0.50), large (0.80), very large (≥ 1.20 for d , ≥ 1.00 for h ) or extremely large (≥ 2.0), in accordance with conventional thresholds. These complementary metrics were employed to provide clinically meaningful insights, especially in light of the limited sample size. 4. Results 4.1 Demographic and Clinical Data Among the 15 patients included in the study, 12 (80%) were female and 3 (20%) were male. Six patients (40%) survived, while nine (60%) died during the follow-up period. The mean age was significantly higher in the non-survivor group compared to the survivor group (57.8 ± 22.8 vs. 29.2 ± 6.9 years, P = 0.029), with a very large effect size (Cohen’s d = 1.56). The mean Glasgow Coma Scale (GCS) score was lower in the non-survivor group (11.1 ± 2.3) compared to the survivor group (13.3 ± 1.6), but the difference did not reach statistical significance ( P = 0.061), although it demonstrated a moderate effect size (Cohen’s d = 0.53)[ 17 ]. Focal neurological deficits were more frequent among non-survivors (67% vs. 17%), with a large effect size (Cohen’s d = 0.94). Cranial nerve involvement was observed more often in non-survivors (56%) than in survivors (33%), with a small effect size (Cohen’s h = 0.47) ( Table 1 ). Table 1 Comparison of Clinical and Demographic Characteristics Between Survivor and Non-Survivor Groups Survivor (n = 6) Non-Survivor (n = 9) P value Age (years) 29.1 ± 6.8 57.78 ± 22.7 0.029 Sex (male) 1 (17) 2 (22) 1.00 Fever 5 (83) 8 (89) 1.00 Headache 5 (83) 5 (56) 0.58 Vomit 4 (67) 4 (44) 0.61 Seizure 2 (33) 4 (44) 1.00 Neurological symptom duration (days) 8.8 ± 4.1 6.7 ± 3.2 0.20 Symptom-treatment duration (days) 9.2 ± 3.9 6.9 ± 3.7 0.20 GCS 13.3 ± 1.6 11.1 ± 2.3 0.06 Meningeal irritation symptom 3 (50) 6 (67) 0.58 Papilledema 2 (33) 4 (44) 1.00 Focal neurological deficit 1 (17) 6 (67) 0.11 * Note: GCS = Glasgow Coma Scale; CNS = Central Nervous System. Values in parentheses are percentage of column 4.2. Cerebrospinal Fluid (CSF) and Laboratory Findings Serum aspartate aminotransferase (AST) levels were significantly higher in the non-survivor group (28.9 ± 6.4 U/L) compared to survivors (15.0 ± 2.9 U/L), with a p value of 0.0067 and an extremely large effect size (Cohen’s d = 2.14). CSF protein levels were also elevated in non-survivors, though not statistically significant ( p > 0.05), but demonstrated a moderate effect size (Cohen’s d = 0.63). Elevated CSF opening pressure(> 15 mmHg) was more frequently observed in non-survivors (67%) than in survivors (33%), indicating a large effect size (Cohen’s d = 0.80). The difference in CSF leukocyte count between the survivor and non-survivor groups was statistically significant ( P = 0.041) and demonstrated a large effect size (Cohen’s d = 0.95), suggesting a clinically meaningful association. Low CSF glucose values were comparable across groups, with a small effect size (Cohen’s h = 0.16). All patients included in the study had positive cerebrospinal fluid (CSF) culture results for Mycobacterium tuberculosis , with 100% culture positivity observed in both the survivor (6/6) and non-survivor (9/9) groups. Antibiotic susceptibility testing (antibiogram) was performed in all culture-positive cases and demonstrated full sensitivity to standard antituberculosis agents across both groups. Polymerase chain reaction (PCR) analysis of CSF specimens yielded positive results in 5 of 6 survivors (83%) and 7 of 9 non-survivors (78%), with no statistically significant difference between groups.In addition to CSF-based diagnostics, PCR positivity in extraparenchymal samples was observed in 78% of non-survivors (7 of 9), while none of the survivors showed positivity in these samples. This difference was statistically significant (P = 0.007), indicating a potentially more disseminated disease profile among non-survivors.All patients underwent HIV serological testing using the ELISA method, and drug susceptibility testing was performed via conventional culture-based antibiogram.Additionally, none of the patients in this cohort tested positive for human immunodeficiency virus (HIV), eliminating HIV-related immunosuppression as a confounding factor in disease severity or mortality ( Table 2 ). Table 2 Comparison of Cerebrospinal Fluid (CSF) and Laboratory Parameters Between Groups. Survivor (n = 6) Non-Survivor (n = 9) P value AST levels (IU/L) 15.0 ± 2.9 28.9 ± 6.4 0.007 CSF appearance (cloudy) 1 (17) 4 (44) 0.62 CSF high pressure(> 15 mmHg) 2 (33) 6 (67) 0.29 CSF leukocyte count (h/mm³) 124.2 ± 36.8 182.3 ± 72.4 0.04 CSF protein (mg/dL) 163 ± 65.1 241 ± 150.2 0.07 CSF glucose count (low values) 5 (83) 8 (89) 1.00 Culture positivity 6 (100) 9 (100) 1.00 Antibiogram sensitivity 6 (100) 9 (100) 1.00 CSF PCR positivity 5 (83) 7 (78) 1.00 PCR positivity outside CSF 0 (0) 7 (78) 0.007 * Note: CSF = Cerebrospinal Fluid Values in parentheses are percentage of column. 4.3. MRI Findings Magnetic resonance imaging (MRI) findings revealed that ventriculitis was observed exclusively in the non-survivor group (11% vs. 0%), demonstrating a very large effect size (Cohen’s h = 1.23). Similarly, cerebral ischemia was detected only in non-survivors (56% vs. 0%), with a statistically significant difference (P = 0.04) and a very large effect size (Cohen’s h = 0.98). The prevalence of encephalitis was also higher among non-survivors (78% vs. 67%) with a moderate effect size (Cohen’s h = 0.62). Cranial nerve involvement (33% vs. 17%) and spinal tuberculosis (11% vs. 0%) were observed only in non-survivors and corresponded to small and moderate effect sizes, respectively (Cohen’s h = 0.39 and 0.68). No statistically significant differences were noted between groups in terms of hydrocephalus, leptomeningeal enhancement, or tuberculoma presence (P > 0.05).(Table 3 and Fig. 1 ). Table 3 Distribution of MRI Findings in Survivor and Non-Survivor Groups. Survivor (n = 6) Non-Survivor (n = 9) P value Hydrocephalus 3 (50) 3 (33) 0.62 Encephalitis 4(67) 7 (78) 1.00 Ventriculitis 0 (0) 1 (11) 1.00 Cerebral ischemia 0 (0) 5 (56) 0.04 Tuberculoma 6 (100) 6 (67) 0.23 Leptomeningeal enhancement 5 (83) 7 (78) 1.00 Cranial nerve involvement 1 (17) 0 (33) 0.6 Spinal involvement 0 (0) 1 (11) 1.00 * Note: MRI = Magnetic Resonance Imaging. Values in parentheses are percentage of column. 4.4. Treatment Process and Clinical Outcomes Standard antituberculosis therapy included isoniazid (5 mg/kg), rifampicin (10 mg/kg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg) for the intensive phase, followed by continuation therapy as per national protocols [ 7 ]. Intravenous dexamethasone was administered (0.3–0.4 mg/kg/day) in cases with marked meningeal enhancement, high CSF pressure, or altered consciousness. VP shunt placement was performed in cases with persistent hydrocephalus, raised intracranial pressure, or deteriorating consciousness despite medical therapy. The frequency of VP shunt procedures was similar between groups (17% in survivors vs. 22% in non-survivors), with no statistically significant difference ( P > 0.05). Likewise, the duration of hospitalization did not differ significantly between survivors and non-survivors (41.8 ± 32.3 vs. 45.6 ± 28.2 days, respectively; P = 0.817). These findings suggest that mortality may be more closely associated with the clinical severity and radiological burden of the disease rather than treatment-related variables (Table 4 ). Table 4 Treatment Process and In-Hospital Outcomes of Patients with CNS-TB. Survivor (n = 6) Non-Survivor (n = 9) P value VP shunt 1 (17) 2 (22) 1.00 Total inpatient time (days) 41.8 ± 32.3 45.6 ± 28.2 0.82 * Note: VP shunt = Ventriculoperitoneal shunt; CNS-TB = Central Nervous System Tuberculosis. Values in parentheses are percentage of column. 4.5. Overall Impression In this study, variables associated with mortality in CNS tuberculosis were evaluated not only in terms of statistical significance but also based on their clinical relevance through effect size analysis. Very large effect sizes were observed for elevated serum AST levels (Cohen’s d = 2.14), older age (Cohen’s d = 1.56), and the presence of ventriculitis (Cohen’s h = 1.23), CSF leukocyte(Cohen’s d = 0.95) indicating strong associations with poor outcomes. Other prominent factors included focal neurological deficits (Cohen’s d = 0.94), increased CSF opening pressure (Cohen’s d = 0.80), and cerebral ischemia (Cohen’s h = 0.98), all of which showed large to very large effect sizes. Notably, some of these parameters did not reach statistical significance due to the limited sample size but demonstrated considerable clinical importance ( Fig. 2 ). 5. Discussion Central nervous system tuberculosis (CNS-TB), although accounting for less than 1% of all tuberculosis cases, remains the extrapulmonary form with the highest mortality rate [ 3 ]. Reported mortality rates vary widely, ranging from 15–60%, influenced by delays in diagnosis, limited access to care, comorbid conditions, and neurological complications [ 4 ]. The 60% mortality rate observed in our cohort likely reflects the relatively older patient population, the severity of radiological findings, and elevated markers of systemic inflammation. Patients in the non-survivor group were significantly older than survivors. Advanced age has been associated with immune senescence and increased prevalence of comorbidities, both of which may contribute to poor outcomes [ 8 , 9 , 10 ]. The very large effect size for age observed in this study reinforces its prognostic importance. Significantly elevated serum AST levels in the non-survivor group with an extremely large effect size suggest a strong association with systemic inflammation and overall disease burden. Similarly, increased CSF opening pressure was more common among non-survivors, likely reflecting intracranial complications such as hydrocephalus or ventriculitis [ 7 , 11 ]. Focal neurological deficits were more frequently observed in non-survivors and demonstrated a large effect size, indicating advanced parenchymal involvement and neurological damage as major predictors of mortality [ 10 ]. MRI findings such as ventriculitis, cerebral ischemia, and encephalitis were found exclusively in non-survivors. Notably, the difference in the frequency of cerebral ischemia reached statistical significance (P = 0.04), supporting its prognostic relevance in line with previous studies[ 12 , 13 ]. Although CSF protein levels were not statistically different between groups, a moderate effect size suggests potential clinical relevance. In contrast, CSF leukocyte count was significantly higher in non-survivors and showed a large effect size, indicating a strong association with poor outcomes. Other CSF markers, such as chloride concentration and glucose levels, showed small effect sizes and may reflect the underlying disease process to a lesser extent. The significantly higher rate of PCR positivity in non-CSF samples among non-survivors may reflect systemic dissemination of tuberculosis, which could contribute to increased disease severity and adverse outcomes. This finding underscores the prognostic importance of extraparenchymal diagnostic evaluation in CNS-TB patients.The findings of Dian et al. [ 14 ] regarding cerebrospinal fluid (CSF) parameters show notable similarities with the results of our study. Both studies emphasize the potential association between increased CSF leukocyte count and protein levels with mortality. This concordance highlights the prognostic value of biochemical and cellular CSF analysis in the evaluation of central nervous system tuberculosis [ 14 ]. No significant differences were observed in VP shunt rates or length of hospital stay between groups, suggesting that clinical severity and imaging findings are more predictive of mortality than treatment-related variables. Although numerous studies in the literature have explored the relationship between HIV co-infection and drug resistance in CNS tuberculosis, none of the patients in our cohort exhibited HIV positivity or drug-resistant strains. This homogeneity may have minimized the confounding effects of immunosuppression and antimicrobial resistance on clinical outcomes [ 15 , 16 ]. The main limitations of this study include its small sample size, single-center design, and retrospective nature. However, the use of both traditional statistical methods and effect size analysis provides a more nuanced understanding of prognostic indicators in CNS-TB and adds value to the interpretation of findings despite limited statistical power. 6. Conclusion In conclusion, factors such as advanced age, elevated AST levels, the presence of focal neurological deficits, increased CSF leukocyte, ventriculitis, cerebral ischemia, and elevated CSF protein concentrations, despite not reaching statistical significance, may still hold clinical relevance and should be considered in prognostic assessments. Incorporating these variables into empirical treatment decisions and intensive care planning may improve patient outcomes. However, prospective, multicenter studies with larger cohorts are required tovalidate the prognostic value of these factors. Declarations Ethicsapprovalandconsentto participate This study was conducted in accordance with the principles of the Declaration of Helsinki.This study was approved by the Ethics Committee of Ege University Faculty of Medicine (Decision No: 25-5T/19, Date: May 8, 2025). The requirement for informed consent to participate was waived by the Ethics Committee of Ege University Faculty of Medicine due to the retrospective nature of the study. Consent for publication Not applicable. Availability of data and materials The data underlying this article will be shared by the corresponding author upon reasonable request. Competing interests The authors declare that they have no actual or potential conflicts of interest. Funding Emre Kumral, Mesut Dorukoğlu, and Zeynep Yamazhan did not receive any funding for this research. Authors' contributions EK: Principal author, study concept and design, data interpretation, supervision. MD: Data acquisition, data interpretation. ZY: Data acquisition. All authors read and approved the final manuscript. Clinical trial number Clinical trial number: not applicable. Consent to participate Informed consent was waived by the ethics committee due to the retrospective nature of the study. Acknowledgements Not applicable. 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Navarro-Flores A, Fernández-Chinguel J, Pacheco-Barrios N, Soriano-Moreno D, Pacheco-Barrios K. Global morbidity and mortality of central nervous system tuberculosis: a systematic review and meta-analysis. J Neurol. 2022;269:3482–94. Dian S, Ganiem A, Van Laarhoven A. Central nervous system tuberculosis. Curr Opin Neurol. 2021;34:396–402. Ayele B, Amogne W. Central Nervous System Tuberculosis (CNS-TB) in treated HIV-infected adults in Tikur Anbessa Specialized Hospital, Ethiopia: A cross sectional study. J Clin Tuberc Other Mycobact Dis. 2021;8:24100252. Alemu A, Bitew Z, Worku T, Gamtesa D, Alebel A. Predictors of mortality in patients with drug-resistant tuberculosis: A systematic review and meta-analysis. PLoS ONE; 2021. p. 16. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81–4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 19 Feb, 2026 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 09 Oct, 2025 Reviews received at journal 27 Sep, 2025 Reviews received at journal 22 Sep, 2025 Reviewers agreed at journal 09 Sep, 2025 Reviewers agreed at journal 07 Sep, 2025 Reviewers agreed at journal 07 Sep, 2025 Reviewers agreed at journal 31 Aug, 2025 Reviewers invited by journal 28 Aug, 2025 Editor assigned by journal 13 Aug, 2025 Editor invited by journal 25 Jul, 2025 Submission checks completed at journal 24 Jul, 2025 First submitted to journal 24 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-7151920","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":509614786,"identity":"8728dd38-bacb-4d2c-b3bb-84fe99091fc0","order_by":0,"name":"Mesut Dorukoğlu","email":"","orcid":"","institution":"Ege University","correspondingAuthor":false,"prefix":"","firstName":"Mesut","middleName":"","lastName":"Dorukoğlu","suffix":""},{"id":509614787,"identity":"994676b2-fd04-41a1-8b8b-0d61249bf29a","order_by":1,"name":"Emre Kumral","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYNCCAyCCufEBhJdAtBbGZgO4lgNEammTIEoLv9jZhw8YzhyONm8/2Fbx4ZcNAz97jgHzxz24tUjOTjc2YLhxOHfOmcS2mzP70hgke94YMBx4hluLwe00NgmGD4dzZzAktt3m7TnMYHAjB6gFj8vsb6ex/wBr4X/YVvy35z+DPSEtBtJpbAwgh82QSGxjZvhxgMFAgoAWidtpzBIJZ9KBWh42S/Y2JPNInHlWcOAMHi38s9MYP3w4Zg10WPLBDz/+2MnxtydvfFCBRwsYJMAYjG0MPCCakAZk8IcEtaNgFIyCUTBiAAC6LFozmOYiewAAAABJRU5ErkJggg==","orcid":"","institution":"Ege University","correspondingAuthor":true,"prefix":"","firstName":"Emre","middleName":"","lastName":"Kumral","suffix":""},{"id":509614788,"identity":"34513dde-24e5-4990-8f91-29a6c73d1e9c","order_by":2,"name":"Zeynep Yamazhan","email":"","orcid":"","institution":"Ege University","correspondingAuthor":false,"prefix":"","firstName":"Zeynep","middleName":"","lastName":"Yamazhan","suffix":""}],"badges":[],"createdAt":"2025-07-17 19:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7151920/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7151920/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-026-04656-4","type":"published","date":"2026-02-19T15:58:38+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90803953,"identity":"390fc1e3-1495-42d5-aa8b-9fadd14f0c2d","added_by":"auto","created_at":"2025-09-08 10:38:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":391440,"visible":true,"origin":"","legend":"\u003cp\u003eMRI Patterns of CNS Tuberculosis\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7151920/v1/76da640faaa5f5bc3aa2992e.png"},{"id":90805242,"identity":"39d1c15a-0c0c-4a53-b3b4-b48b753b3b1f","added_by":"auto","created_at":"2025-09-08 10:46:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":120413,"visible":true,"origin":"","legend":"\u003cp\u003eRanked Effect Sizes of Clinical, Laboratory, and Radiological Predictors of Mortality in CNS Tuberculosis\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7151920/v1/5130597db5410cb8983926e6.png"},{"id":103251235,"identity":"37480087-87d7-45d9-b907-03614f3d5d49","added_by":"auto","created_at":"2026-02-23 16:06:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1214889,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7151920/v1/564bae81-8286-4659-b10b-5de917cce06a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictors of Mortality in CNS Tuberculosis: Clinical and Radiological Parameters","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eTuberculosis (TB) remains a critical global health issue despite advances in diagnosis and treatment. According to the World Health Organization's 2022 Global Tuberculosis Report, an estimated 10.6\u0026nbsp;million people were diagnosed with TB in 2021, and approximately 1.3\u0026nbsp;million died, underscoring the disease\u0026rsquo;s persistent threat, particularly in resource-limited settings and among immunocompromised individuals such as those with HIV infection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWhile pulmonary TB is the most common form, extrapulmonary tuberculosis (EPTB) accounts for nearly one-third of all TB cases, and among these, central nervous system tuberculosis (CNS-TB) represents the most severe and life-threatening manifestation, comprising approximately 5\u0026ndash;10% of EPTB cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The CNS can be affected by tuberculous meningitis, tuberculomas, abscesses, encephalitis, or spinal involvement, each carrying substantial risk for disability and death.\u003c/p\u003e\u003cp\u003eMortality rates in CNS-TB remain high, ranging from 15\u0026ndash;60% in published cohorts, depending on factors such as age, immune status, comorbidities, and access to early diagnosis and appropriate therapy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In Turkey, CNS-TB is rare but still seen in tertiary centers, particularly among populations with socioeconomic challenges or latent TB reactivation.\u003c/p\u003e\u003cp\u003eThe diagnosis of CNS-TB is challenging due to the nonspecific nature of early symptoms and the limited sensitivity of conventional diagnostic methods such as CSF microscopy and culture. While CSF culture remains the gold standard, its low positivity rate and prolonged turnaround time necessitate reliance on radiological findings and empirical clinical judgment in many cases [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Delays in diagnosis often result in patients presenting in advanced disease stages, where complications like hydrocephalus, infarction, and altered consciousness are common.\u003c/p\u003e\u003cp\u003eTo assist clinicians in evaluating disease severity and prognosis, several staging and scoring systems have been developed. The British Medical Research Council (BMRC) grading classifies CNS-TB severity based on consciousness and focal deficits, and more recent models incorporate Glasgow Coma Scale (GCS), CSF parameters, and comorbid conditions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nevertheless, there is still a lack of consensus on reliable predictors of mortality, especially when considering combined clinical, laboratory, and neuroimaging findings.\u003c/p\u003e\u003cp\u003eThis study aimed to determine the prognostic significance of specific clinical, laboratory, and neuroimaging parameters\u0026mdash;such as age, liver enzyme levels, CSF indices, and MRI abnormalities\u0026mdash;in relation to mortality in CNS-TB. By comparing survivors and non-survivors, we sought to identify early predictors that could inform intervetion strategies.\u003c/p\u003e"},{"header":"2. Materials andMethods","content":"\u003cp\u003eThis retrospective observational study included 15 patients diagnosed with central nervous system tuberculosis (CNS-TB) who were followed between January 2010 and January 2023 in the neurology and infectious diseases departments of a tertiary university hospital. Diagnosis was made based on the criteria proposed by Marais et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and national guidelines [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], including at least two of the following: typical clinical features (e.g., headache, fever, altered consciousness), CSF findings suggestive of TB (high protein, low glucose, pleocytosis), positive neuroimaging, or microbiological confirmation (culture or PCR).Patient data were retrospectively reviewed from electronic hospital records. A structured data collection form was used to extract information including demographic characteristics, presenting symptoms, neurological examination findings, CSF biochemistry, neuroimaging results, and treatment details. Based on clinical outcomes, patients were categorized into two groups: survivors (n\u0026thinsp;=\u0026thinsp;6) and non-survivors (n\u0026thinsp;=\u0026thinsp;9).\u003c/p\u003e\u003cp\u003eCSF parameters analyzed included leukocyte count, protein, glucose, chloride levels, and opening pressure. Additional laboratory results such as CSF culture, PCR, and antibiogram sensitivity were also recorded. MRI findings such as meningeal contrast enhancement, hydrocephalus, tuberculoma, ventriculitis, cerebral ischemia, and cranial nerve involvement were evaluated for all patients.\u003c/p\u003e\u003cp\u003eAll patients received standardized antituberculosis therapy consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol, initiated immediately after diagnosis. Intravenous corticosteroid therapy (dexamethasone) was administered in patients with significant meningeal involvement or clinical indications. Neurosurgical interventions, such as ventriculoperitoneal shunt placement, were performed when necessary based on clinical and radiological indications.\u003c/p\u003e\u003cp\u003e This study was approved by the Ethics Committee of Ege University Faculty of Medicine.\u003c/p\u003e"},{"header":"3. Statistical Analysis","content":"\u003cp\u003eStatistical analyses were conducted using SPSS software version 26.0 (IBM Corp., Armonk, NY, USA). The distribution of continuous variables was assessed using the Shapiro\u0026ndash;Wilk test. Normally distributed data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, while non-normally distributed variables were reported as median with minimum and maximum values. Categorical variables were summarized as frequencies and percentages. For comparisons between survivor and non-survivor groups, independent samples t-tests were used for normally distributed continuous variables, and the Mann\u0026ndash;Whitney U test was applied for non-normally distributed data. Categorical variables were compared using Pearson\u0026rsquo;s chi-square test or Fisher\u0026rsquo;s exact test, depending on expected cell counts. To assess the magnitude of group differences beyond statistical significance, effect size analyses were performed using Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e for continuous variables and Cohen\u0026rsquo;s \u003cem\u003eh\u003c/em\u003e for proportions. Effect sizes were interpreted as small (0.20), medium (0.50), large (0.80), very large (\u0026ge;\u0026thinsp;1.20 for \u003cem\u003ed\u003c/em\u003e, \u0026ge;\u0026thinsp;1.00 for \u003cem\u003eh\u003c/em\u003e) or extremely large (\u0026ge;\u0026thinsp;2.0), in accordance with conventional thresholds. These complementary metrics were employed to provide clinically meaningful insights, especially in light of the limited sample size.\u003c/p\u003e"},{"header":"4. Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e4.1 Demographic and Clinical Data\u003c/h2\u003e\u003cp\u003eAmong the 15 patients included in the study, 12 (80%) were female and 3 (20%) were male. Six patients (40%) survived, while nine (60%) died during the follow-up period. The mean age was significantly higher in the non-survivor group compared to the survivor group (57.8\u0026thinsp;\u0026plusmn;\u0026thinsp;22.8 vs. 29.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9 years, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029), with a very large effect size (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.56). The mean Glasgow Coma Scale (GCS) score was lower in the non-survivor group (11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3) compared to the survivor group (13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6), but the difference did not reach statistical significance (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.061), although it demonstrated a moderate effect size (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.53)[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Focal neurological deficits were more frequent among non-survivors (67% vs. 17%), with a large effect size (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.94). Cranial nerve involvement was observed more often in non-survivors (56%) than in survivors (33%), with a small effect size (Cohen\u0026rsquo;s \u003cem\u003eh\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.47) \u003cem\u003e(\u003c/em\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cem\u003e).\u003c/em\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\u003eComparison of Clinical and Demographic Characteristics Between Survivor and Non-Survivor Groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurvivor (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-Survivor (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57.78\u0026thinsp;\u0026plusmn;\u0026thinsp;22.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (male)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFever\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeadache\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVomit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSeizure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeurological symptom duration (days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSymptom-treatment duration (days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGCS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningeal irritation symptom\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePapilledema\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFocal neurological deficit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003e*\u003c/b\u003e Note: GCS\u0026thinsp;=\u0026thinsp;Glasgow Coma Scale; CNS\u0026thinsp;=\u0026thinsp;Central Nervous System.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues in parentheses are percentage of column\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e4.2. Cerebrospinal Fluid (CSF) and Laboratory Findings\u003c/h2\u003e\u003cp\u003eSerum aspartate aminotransferase (AST) levels were significantly higher in the non-survivor group (28.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 U/L) compared to survivors (15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 U/L), with a \u003cem\u003ep\u003c/em\u003e value of 0.0067 and an extremely large effect size (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.14). CSF protein levels were also elevated in non-survivors, though not statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), but demonstrated a moderate effect size (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.63). Elevated CSF opening pressure(\u0026gt;\u0026thinsp;15 mmHg) was more frequently observed in non-survivors (67%) than in survivors (33%), indicating a large effect size (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.80). The difference in CSF leukocyte count between the survivor and non-survivor groups was statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041) and demonstrated a large effect size (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.95), suggesting a clinically meaningful association. Low CSF glucose values were comparable across groups, with a small effect size (Cohen\u0026rsquo;s \u003cem\u003eh\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16). All patients included in the study had positive cerebrospinal fluid (CSF) culture results for \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e, with 100% culture positivity observed in both the survivor (6/6) and non-survivor (9/9) groups. Antibiotic susceptibility testing (antibiogram) was performed in all culture-positive cases and demonstrated full sensitivity to standard antituberculosis agents across both groups. Polymerase chain reaction (PCR) analysis of CSF specimens yielded positive results in 5 of 6 survivors (83%) and 7 of 9 non-survivors (78%), with no statistically significant difference between groups.In addition to CSF-based diagnostics, PCR positivity in extraparenchymal samples was observed in 78% of non-survivors (7 of 9), while none of the survivors showed positivity in these samples. This difference was statistically significant (P\u0026thinsp;=\u0026thinsp;0.007), indicating a potentially more disseminated disease profile among non-survivors.All patients underwent HIV serological testing using the ELISA method, and drug susceptibility testing was performed via conventional culture-based antibiogram.Additionally, none of the patients in this cohort tested positive for human immunodeficiency virus (HIV), eliminating HIV-related immunosuppression as a confounding factor in disease severity or mortality \u003cem\u003e(\u003c/em\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cem\u003e).\u003c/em\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\u003eComparison of Cerebrospinal Fluid (CSF) and Laboratory Parameters Between Groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurvivor (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-Survivor (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST levels (IU/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF appearance (cloudy)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF high pressure(\u0026gt;\u0026thinsp;15 mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF leukocyte count (h/mm\u0026sup3;)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e124.2\u0026thinsp;\u0026plusmn;\u0026thinsp;36.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e182.3\u0026thinsp;\u0026plusmn;\u0026thinsp;72.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF protein (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e163\u0026thinsp;\u0026plusmn;\u0026thinsp;65.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e241\u0026thinsp;\u0026plusmn;\u0026thinsp;150.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF glucose count (low values)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCulture positivity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntibiogram sensitivity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF PCR positivity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePCR positivity outside CSF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003e*\u003c/b\u003eNote: CSF\u0026thinsp;=\u0026thinsp;Cerebrospinal Fluid\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues in parentheses are percentage of column.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e\u003cem\u003e4.3.\u003c/em\u003eMRI Findings\u003c/h2\u003e\u003cp\u003eMagnetic resonance imaging (MRI) findings revealed that ventriculitis was observed exclusively in the non-survivor group (11% vs. 0%), demonstrating a very large effect size (Cohen\u0026rsquo;s h\u0026thinsp;=\u0026thinsp;1.23). Similarly, cerebral ischemia was detected only in non-survivors (56% vs. 0%), with a statistically significant difference (P\u0026thinsp;=\u0026thinsp;0.04) and a very large effect size (Cohen\u0026rsquo;s h\u0026thinsp;=\u0026thinsp;0.98). The prevalence of encephalitis was also higher among non-survivors (78% vs. 67%) with a moderate effect size (Cohen\u0026rsquo;s h\u0026thinsp;=\u0026thinsp;0.62). Cranial nerve involvement (33% vs. 17%) and spinal tuberculosis (11% vs. 0%) were observed only in non-survivors and corresponded to small and moderate effect sizes, respectively (Cohen\u0026rsquo;s h\u0026thinsp;=\u0026thinsp;0.39 and 0.68). No statistically significant differences were noted between groups in terms of hydrocephalus, leptomeningeal enhancement, or tuberculoma presence (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).(Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cem\u003eand\u003c/em\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cem\u003e).\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDistribution of MRI Findings in Survivor and Non-Survivor Groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurvivor (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-Survivor (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHydrocephalus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEncephalitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4(67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVentriculitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebral ischemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTuberculoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeptomeningeal enhancement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCranial nerve involvement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSpinal involvement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003e*\u003c/b\u003eNote: MRI\u0026thinsp;=\u0026thinsp;Magnetic Resonance Imaging.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues in parentheses are percentage of column.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e4.4. Treatment Process and Clinical Outcomes\u003c/h2\u003e\u003cp\u003eStandard antituberculosis therapy included isoniazid (5 mg/kg), rifampicin (10 mg/kg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg) for the intensive phase, followed by continuation therapy as per national protocols [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Intravenous dexamethasone was administered (0.3\u0026ndash;0.4 mg/kg/day) in cases with marked meningeal enhancement, high CSF pressure, or altered consciousness. VP shunt placement was performed in cases with persistent hydrocephalus, raised intracranial pressure, or deteriorating consciousness despite medical therapy. The frequency of VP shunt procedures was similar between groups (17% in survivors vs. 22% in non-survivors), with no statistically significant difference (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Likewise, the duration of hospitalization did not differ significantly between survivors and non-survivors (41.8\u0026thinsp;\u0026plusmn;\u0026thinsp;32.3 vs. 45.6\u0026thinsp;\u0026plusmn;\u0026thinsp;28.2 days, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.817). These findings suggest that mortality may be more closely associated with the clinical severity and radiological burden of the disease rather than treatment-related variables (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTreatment Process and In-Hospital Outcomes of Patients with CNS-TB.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurvivor (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-Survivor (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003evalue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVP shunt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal inpatient time (days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41.8\u0026thinsp;\u0026plusmn;\u0026thinsp;32.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.6\u0026thinsp;\u0026plusmn;\u0026thinsp;28.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.82\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003e*\u003c/b\u003eNote: VP shunt\u0026thinsp;=\u0026thinsp;Ventriculoperitoneal shunt; CNS-TB\u0026thinsp;=\u0026thinsp;Central Nervous System Tuberculosis.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues in parentheses are percentage of column.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e4.5. Overall Impression\u003c/h2\u003e\u003cp\u003eIn this study, variables associated with mortality in CNS tuberculosis were evaluated not only in terms of statistical significance but also based on their clinical relevance through effect size analysis. Very large effect sizes were observed for elevated serum AST levels (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.14), older age (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.56), and the presence of ventriculitis (Cohen\u0026rsquo;s \u003cem\u003eh\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.23), CSF leukocyte(Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.95) indicating strong associations with poor outcomes. Other prominent factors included focal neurological deficits (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.94), increased CSF opening pressure (Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.80), and cerebral ischemia (Cohen\u0026rsquo;s \u003cem\u003eh\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.98), all of which showed large to very large effect sizes. Notably, some of these parameters did not reach statistical significance due to the limited sample size but demonstrated considerable clinical importance\u003c/p\u003e\u003cp\u003e\u003cem\u003e(\u003c/em\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cem\u003e).\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"5. Discussion","content":"\u003cp\u003eCentral nervous system tuberculosis (CNS-TB), although accounting for less than 1% of all tuberculosis cases, remains the extrapulmonary form with the highest mortality rate [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Reported mortality rates vary widely, ranging from 15\u0026ndash;60%, influenced by delays in diagnosis, limited access to care, comorbid conditions, and neurological complications [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The 60% mortality rate observed in our cohort likely reflects the relatively older patient population, the severity of radiological findings, and elevated markers of systemic inflammation.\u003c/p\u003e\u003cp\u003ePatients in the non-survivor group were significantly older than survivors. Advanced age has been associated with immune senescence and increased prevalence of comorbidities, both of which may contribute to poor outcomes [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The very large effect size for age observed in this study reinforces its prognostic importance.\u003c/p\u003e\u003cp\u003eSignificantly elevated serum AST levels in the non-survivor group with an extremely large effect size suggest a strong association with systemic inflammation and overall disease burden. Similarly, increased CSF opening pressure was more common among non-survivors, likely reflecting intracranial complications such as hydrocephalus or ventriculitis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFocal neurological deficits were more frequently observed in non-survivors and demonstrated a large effect size, indicating advanced parenchymal involvement and neurological damage as major predictors of mortality [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. MRI findings such as ventriculitis, cerebral ischemia, and encephalitis were found exclusively in non-survivors. Notably, the difference in the frequency of cerebral ischemia reached statistical significance (P\u0026thinsp;=\u0026thinsp;0.04), supporting its prognostic relevance in line with previous studies[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough CSF protein levels were not statistically different between groups, a moderate effect size suggests potential clinical relevance. In contrast, CSF leukocyte count was significantly higher in non-survivors and showed a large effect size, indicating a strong association with poor outcomes. Other CSF markers, such as chloride concentration and glucose levels, showed small effect sizes and may reflect the underlying disease process to a lesser extent. The significantly higher rate of PCR positivity in non-CSF samples among non-survivors may reflect systemic dissemination of tuberculosis, which could contribute to increased disease severity and adverse outcomes. This finding underscores the prognostic importance of extraparenchymal diagnostic evaluation in CNS-TB patients.The findings of Dian et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] regarding cerebrospinal fluid (CSF) parameters show notable similarities with the results of our study. Both studies emphasize the potential association between increased CSF leukocyte count and protein levels with mortality. This concordance highlights the prognostic value of biochemical and cellular CSF analysis in the evaluation of central nervous system tuberculosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. No significant differences were observed in VP shunt rates or length of hospital stay between groups, suggesting that clinical severity and imaging findings are more predictive of mortality than treatment-related variables.\u003c/p\u003e\u003cp\u003eAlthough numerous studies in the literature have explored the relationship between HIV co-infection and drug resistance in CNS tuberculosis, none of the patients in our cohort exhibited HIV positivity or drug-resistant strains. This homogeneity may have minimized the confounding effects of immunosuppression and antimicrobial resistance on clinical outcomes [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe main limitations of this study include its small sample size, single-center design, and retrospective nature. However, the use of both traditional statistical methods and effect size analysis provides a more nuanced understanding of prognostic indicators in CNS-TB and adds value to the interpretation of findings despite limited statistical power.\u003c/p\u003e"},{"header":"6. Conclusion","content":"\u003cp\u003eIn conclusion, factors such as advanced age, elevated AST levels, the presence of focal neurological deficits, increased CSF leukocyte, ventriculitis, cerebral ischemia, and elevated CSF protein concentrations, despite not reaching statistical significance, may still hold clinical relevance and should be considered in prognostic assessments. Incorporating these variables into empirical treatment decisions and intensive care planning may improve patient outcomes. However, prospective, multicenter studies with larger cohorts are required tovalidate the prognostic value of these factors.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthicsapprovalandconsentto participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki.This study was approved by the Ethics Committee of Ege University Faculty of Medicine (Decision No: 25-5T/19, Date: May 8, 2025). The requirement for informed consent to participate was waived by the Ethics Committee of Ege University Faculty of Medicine due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this article will be shared by the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no actual or potential conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEmre Kumral, Mesut Dorukoğlu, and Zeynep Yamazhan did not receive any funding for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEK: Principal author, study concept and design, data interpretation, supervision.\u003cbr\u003e MD: Data acquisition, data interpretation.\u003cbr\u003e ZY: Data acquisition.\u003cbr\u003e All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was waived by the ethics committee due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Microbiol Rev. 2008;21(2):243\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThwaites GE, Chau TTH, Mai NTH, Drobniewski F, McAdam KPWJ, Farrar JJ. Tuberculous meningitis. J Neurol NeurosurgPsychiatry. 2000;68(3):289\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCherian A, Thomas SV. Central nervous system tuberculosis. Curr Neurol Neurosci Rep. 2011;11(6):512\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarais S, Thwaites G, Schoeman JF, Torok ME, Misra UK, Prasad K, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010;10(11):803\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHeemskerk AD, Bang ND, Mai NTH, Chau TTH, Phu NH, Loc PP, et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med. 2016;374(2):124\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhuja GK, Mohan KK, Prasad K, Behari M, Chopra JS. Diagnostic criteria for tuberculous meningitis and their validation. Tuber Lung Dis. 1994;75(2):149\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRepublic of Turkey Ministry of Health. General Directorate of Public Health (2019)Tuberculosis Diagnosis and Treatment Guidelines. Ankara.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCorbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, Dye C. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med. 2003;163(9):1009\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHarries AD, Zachariah R, Lawn SD. Providing HIV care for co-infected tuberculosis patients: a perspective from sub-Saharan Africa. Int J Tuberc Lung Dis. 2009;13(1):6\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMisra UK, Kalita J, Nair PP. Diagnostic and prognostic markers in tuberculous meningitis. J Neurol Sci. 2000;181(1\u0026ndash;2):48\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSahly H, Teeter L, Pan X, Musser J, Graviss E. Mortality associated with central nervous system tuberculosis. J Infect. 2007;55(6):502\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbdelmalek MF, Gharib MI, Amin MA. MRI of central nervous system tuberculosis: spectrum of findings and diagnostic pitfalls. Egypt J Radiol Nuclear Med. 2006;37(2):431\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNavarro-Flores A, Fern\u0026aacute;ndez-Chinguel J, Pacheco-Barrios N, Soriano-Moreno D, Pacheco-Barrios K. Global morbidity and mortality of central nervous system tuberculosis: a systematic review and meta-analysis. J Neurol. 2022;269:3482\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDian S, Ganiem A, Van Laarhoven A. Central nervous system tuberculosis. Curr Opin Neurol. 2021;34:396\u0026ndash;402.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAyele B, Amogne W. Central Nervous System Tuberculosis (CNS-TB) in treated HIV-infected adults in Tikur Anbessa Specialized Hospital, Ethiopia: A cross sectional study. J Clin Tuberc Other Mycobact Dis. 2021;8:24100252.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlemu A, Bitew Z, Worku T, Gamtesa D, Alebel A. Predictors of mortality in patients with drug-resistant tuberculosis: A systematic review and meta-analysis. PLoS ONE; 2021. p. 16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTeasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"CNS tuberculosis, mortality, outcome, risk factors","lastPublishedDoi":"10.21203/rs.3.rs-7151920/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7151920/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eCentral nervous system tuberculosis (CNS-TB) is a rare but highly lethal form of tuberculosis with variable clinical and radiological presentations. This study aimed to identify clinical, laboratory, and neuroimaging parameters associated with mortality in CNS-TB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eIn this retrospective study, 15 patients diagnosed with CNS-TB between 2010 and 2023 were divided into survivors (n = 6) and non-survivors (n = 9). Demographic, clinical, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) data were analyzed. Statistical comparisons and effect size analyses (Cohen’s d, h) were performed to assess clinical significance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe mortality rate was 60%. Non-survivors were significantly older (57.8 ± 22.8 vs. 29.2 ± 6.9 years; P = 0.029, d = 1.56) and had higher serum AST levels (28.9 ± 6.4 vs. 15.0 ± 2.9 U/L; P = 0.007, d = 2.14). CSF leukocyte count was also significantly elevated in non-survivors (P = 0.041, d = 0.95). Cerebral ischemia was present only in non-survivors (56% vs. 0%; P = 0.04, h = 0.98). PCR positivity in non-CSF samples (0% vs. 78%) was significantly associated with mortality (P = 0.007). Other parameters showing moderate to large effect sizes included focal neurological deficits, ventriculitis, and increased CSF opening pressure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eAdvanced age, elevated AST levels, increased CSF leukocyte count, cerebral ischemia, and extraparenchymal PCR positivity emerged as major predictors of mortality in CNS-TB. These factors may aid early risk stratification and treatment planning. Larger prospective studies are warranted to validate these findings.\u003c/p\u003e","manuscriptTitle":"Predictors of Mortality in CNS Tuberculosis: Clinical and Radiological Parameters","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-08 10:38:03","doi":"10.21203/rs.3.rs-7151920/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-09T07:40:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-27T19:36:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-22T11:45:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331864605526955972603616692772303348841","date":"2025-09-10T01:53:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329566455439109247166826429006875085458","date":"2025-09-07T17:10:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"204045166867236986503652958711875139143","date":"2025-09-07T04:30:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"260244986595229040921949093491902599706","date":"2025-08-31T15:40:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-28T17:54:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-13T04:31:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-25T08:04:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-24T11:10:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-07-24T11:07:39+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":"d4a32d8b-48bb-4125-9b45-3d0e199043c6","owner":[],"postedDate":"September 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T16:03:45+00:00","versionOfRecord":{"articleIdentity":"rs-7151920","link":"https://doi.org/10.1186/s12883-026-04656-4","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2026-02-19 15:58:38","publishedOnDateReadable":"February 19th, 2026"},"versionCreatedAt":"2025-09-08 10:38:03","video":"","vorDoi":"10.1186/s12883-026-04656-4","vorDoiUrl":"https://doi.org/10.1186/s12883-026-04656-4","workflowStages":[]},"version":"v1","identity":"rs-7151920","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7151920","identity":"rs-7151920","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}