High blood neutrophil-lymphocyte ratio associated with short poor outcome in tuberculous meningitis

High blood neutrophil-lymphocyte ratio associated with short poor outcome in tuberculous meningitis | 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 High blood neutrophil-lymphocyte ratio associated with short poor outcome in tuberculous meningitis Zhihan Gu, Bofu Liu, Xiaomin YU, Tao Cheng, Tianyong Han, Le Tong, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2042550/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Jul, 2023 Read the published version in BMC Infectious Diseases → Version 1 posted 9 You are reading this latest preprint version Abstract Background It is difficult to predict the short prognosis of tuberculous meningitis (TBM), no study reported the neutrophil lymphocyte ratio(NLR) as a predictor of short prognosis in TBM and the relationship between NLR and the severity of TBM. We hypothesized that NLR is an indicator to reflect independent prognostic significance in patients with TBM and there is a correlation between NLR and the severity of TBM. This study aimed to know the role of the neutrophil lymphocyte ratio as a predictor of 28-mortality and the relationship with the severity of TBM in patients with TBM. Methods We retrospectively collected data from patients diagnosed with TBM in the West China Hospital, Sichuan University, from the period bet w een January 1st, 2018 and August 1st, 2019. Multivariable analysis was executed by the logistic regression model to verify the independence of the 28-day mortality, Spearman correlation analysis was performed to discuss correlation about and the severity of TBM. Results A total of 231 patients were enrolled. 68 (29.4%) patients were classified as stage I. 142(61.5%) patients were stage II.25(10.8) patients were stage III. 16(6.9%) patients died during the follow-up period of 28 days. By multiple logistic regression analyses, the NLR(OR = 1.066, 95% CI = 1.002–1.133, p = 0.043), peripheral neurological deficit (OR 7.485, 95% CI2.010-27.876, P = 0 .003)and hydrocephalus (OR 11.329, 95% CI 2.395–53.583, P = 0 .002) were associated with the independent risks of 28-day mortality. Spearman correlation analysis showed the severity of TBM was significantly positively correlated with the NLR(r = 0.216, p = 0.01). Conclusions NLR, peripheral neurological deficit and hydrocephalus were independent predictors of short prognosis and NLR was significantly positively correlated with the severity of TBM. Tuberculous meningitis neutrophil-lymphocyte ratio(NLR) prognosis Figures Figure 1 Figure 2 Figure 3 Introduction Tuberculosis (TB) is the major cause of death by an infectious disease around the global[ 1 ],but tuberculous meningitis (TBM) is the most devastating manifestation of infection with mycobacterium tuberculosis[ 2 ]. TBM is a kind of inflammation caused by Mycobacterium tuberculosis invading the human central nervous system (including the spinal cord or meninges or brain parenchyma) and then form a series of secondary pathophysiological change in patients’ brain[ 3 ].The clinical course of TBM is nonspecific and quite variable, it is difficult to predict a prognosis early in the disease. But early identification of high-risk patients with poor prognosis and intensive treatment may improve prognosis of TBM[ 4 ]. So, early assessment of the risk factor in patients with TBM is crucial in making clinical decisions. Even given anti-tuberculosis treatment, The mortality rate of TBM patients as high as 10–50%[ 5 ]. Some studies indicated that factors such as disturbance of consciousness and hydrocephalus might be correlated with poor outcome for patients with TBM [ 2 , 5 , 6 ]. However, the marker of inflammation in the blood has not be reported about the short prognosis of TBM patients. Neutrophil-lymphocyte ratio (NLR) is defined as the number of neutrophils in whole blood divided by the number of lymphocytes in whole blood[ 7 ],it is a biomarker derived from leukocytes as a marker of inflammation. The NLR describes is a reliable parameter to describe the immune response to various stimuli/stressors[ 8 ] and has been found to be a useful biomarker for predicting mortality in various clinical setting including sepsis, miliary tuberculosis and bacterial meningitis [ 8 – 10 ],but the association of NLR with clinical outcome in patients with TBM has not been reported, This study is expected to explain the role of NLR as a predictor of short prognosis in patients with TBM. Methods Patients and diagnosis of TBM We retrospectively collected the data of all patients ( > = 15year-old) who were admitted to the West China Hospital, Sichuan University and diagnosed with TBM, from the period bet w een January 1st, 2018 and August 1st, 2019. Patients were eligible for inclusion according to the standardized case definition of TBM proposed by Marais including the clinical criteria, CSF criteria, cerebral imaging criteria, evidence of tuberculosis elsewhere and exclusion of alternative diagnoses: An alternative diagnosis must be confirmed microbiologically, serologically, or histopathologically[ 11 ]. Patients with data was insufficient and pregnant was excluded from the study. Collection of clinical data The data information of patients was obtained by the patients’ electronic medical record management system and telephone. The data included Demographic data(gender, age, duration of illness, HIV-infected), the clinical criteria (fever(> 37.5℃) > 5days, night sweats, weight loss, cough, headache, vomiting, peripheral nerve dysfunction, cognitive impairment, change of consciousness, cranial nerve paralysis, seizures), laboratory data (red blood cell counts, white blood cell counts, platelet, plasma sodium, plasma potassium, plasma glucose, albumin ,CSF cells, CSF protein, CSF glucose, CSF to plasma glucose ratio, CSF chlorine)and cerebral imaging criteria (Hydrocephalus、Basal meningeal enhancement、Tuberculoma、Infarct)were collected based on the first available data at the time of admission and included complete blood cell counts .We also collected the outcome (survivors and non-survivors) after 28 day and the severity of TBM at the time of admission which was assessed using the British Medical Research Council (BMRC) TBM stages. this was modified as grade I (GCS 15; no focal neurological signs), grade II (GCS 11–14, or 15 with focal neurological signs), and grade III (GCS ≤ 10) disease.[ 11 ] Management Patients received four TBM treatments, isoniazid (10–20 mg/day; maximum 1200 mg/day), rifampicin (10–20 mg/day; maximum 600 mg/day), pyrazinamide (20–30 mg/day; maximum 1500 mg/ day), and ethambutol: (15–20 mg/day; maximum 750 mg/day), they also received dexamethasone during early treatment. Statistical analysis A chi-squared or Fisher’s exact test was implemented to compare the categorical variables. An independent-sample test was utilized to compare the continuous variables. Multivariable analysis was executed by the logistic regression model to verify the independence of the 28-day mortality, and the Lemeshow-Hosmer χ2 statistics was used to evaluate the Goodness-of-fit of the model. Discrimination power of for predicting 28-day mortality was assessed via Receiver Operating Characteristic (ROC) curve. Spearman correlation analysis was performed to discuss correlation about and the severity of TBM. All statistical analyses were implemented with the use of SPSS software version 22.0 (USA, IBM analytics). A P value equal or less than 0.05 was statistically significant in all analyses. Results There were 245 patients with TBM who were treated at the West China Hospital, Sichuan University. 14 patients were excluded from the study, among them, 10 patients had insufficient data and 4 patients were pregnant, finally, a total of 231 patients were analyzed in this study. there were 16 (6.95) patients who died in this study period and the remaining 215(93.1%) patients survived. In the study, there are 130 (56.3%) men and 105 (43.7%) women. The mean age was 36.4 ± 16.7years (range 15–78years),4 patients are HIV-infected who are survivors, The patients were divided into three stages according to the severity: 68 (29.4%) patients were classified as stage I; 142(61.5%) patients were stage II, among them;25(10.8%) patients were stage III(Fig. 1 ). Table 1 describes the patients' characteristics between the between survivors and non-survivors. NLR was higher in the non-survivors compared with survivors (P = 0.002), but albumin was lower in the non-survivors(P = 0.05). TBM patients with survivors had more Peripheral neurological deficit (P＜0.001), loss of consciousness (P = 0.003), and hydrocephalus(P＜0.001) than non-survivors patients. There was no significant statistical difference in the other factors. Multivariate logistic regression models (Table 2 ) indicated that the NLR was associated with the independent risks of 28-day mortality(OR = 1.066, 95% CI = 1.002–1.133, p = 0.043), meanwhile, the non-survivors patients were significantly more likely to have peripheral neurological deficit (OR 7.485, 95% CI2.010-27.876, P = 0 .003)and hydrocephalus (OR 11.329, 95% CI 2.395–53.583, P = 0 .002)than survivors patients. There were no differences in the rate of loss of consciousness and in the level of albumin. The Hosmer-Lemeshowχ2 statistics of the univariate logistic regression models was1.260 ( P = 0.996). The area under the curve (AUC) of the ROC curves predicting 28-day mortality for patients with TBM of the NLR was 0.687 (95% CI 0.546–0.828, p = 0.013), the optimal cut off result is 5.225. By using a cutoff point of 9.9904, the NLR has a sensitivity of 56.3% and a specificity of 81.3% (Fig. 2 ). The Study explored the relationship between the severity of TBM and the NLR. The NLR was 6.00 ± 5.03 when the patients were in stage I, the NLR was 7.43 ± 6.92when the patients were in stage II, the NLR was 12.00 ± 9.92when the patients were in stage III(Fig. 3 ). Spearman correlation analysis showed the severity of TBM was significantly positively correlated with the NLR (r = 0.216, p = 0.01). Discussion IN the study, NLR is an independent predictor for short prognosis in patients with TBM. NLR is an inflammatory marker that can be obtained simply and fast. NLR represents the relative neutrophil elevation or lymphocyte decrease. A number of studies have reported that high NLR is associated with high mortality in cancers[ 12 – 14 ] or cardiovascular diseases[ 9 , 15 , 16 ]. In this study, association of high NLR with high severity of TBM is also represented as some study has reported that high NLR may have a higher cancer stage[ 13 , 17 , 18 ] or the severity of pulmonary TB[ 19 ]. At present, the cause for the correlation between the increase in NLR and poor outcome has not yet been explained clearly. High neutrophil counts or lymphopenia may be associated with poor prognosis in several previous studies on TB[ 18 , 20 , 21 ], but NLR has not been represented in the patients with TBM. Chedid, C hypothesized that high neutrophil counts and low lymphocyte proportions had highly inflammatory clinical patterns by the context of mycobacterial infection[ 20 ], which are markers of persisting inflammation or failure to clear the bacteria [ 22 ]. High neutrophil counts may reflect the presence of delayed apoptosis in inflammatory condition, and inhibit the anti-inflammatory ability of neutrophil cells[ 23 ]. In chronic TB infection, sustained inflammation which was an impairment maker of the TB-specific immune response and a marker of active disease has be reported[ 24 ]. High NLR may represent relative lymphopenia, low lymphocyte counts are associated with a negative response to treatment[ 20 , 25 ]in relation to cell-mediated immunity which is important in the immune response to M. tuberculosis[ 9 ]. So, the similar pathway may have affected the progression and prognosis of TBM. In this study, peripheral neurological deficit is a predictor of poor outcome in patients with TBM. A series of studies had reported similar conclusion [ 26 – 28 ]. About 15–50% of patients with TBM have exist peripheral neurological deficit when they first present symptom[ 27 – 30 ],this study reported 30% (69/231) of patients with TBM. This condition may be associated with high rates of morbidity and mortality. Some studies also reported cranial nerve palsy is a risk factors association with bad outcome[ 30 , 31 ],but this study did not support it. this study focused the 28-day mortality however those studies had a long-term follow-up result. Hydrocephalus is a quite common complication of TBM, as reported, up to 60% of patients with TBM be found to by cranial imaging such as MRI/CT[ 32 ]. hydrocephalus of TBM may be associated a pathogenesis of meningeal exudate and either overproduction of CSF or malfunctioning absorption of CSF in the subarachnoid space[ 33 , 34 ],and is thought to be an important risk factor of poor outcome. the V-P shunt, or CSF drainage is a management way of hydrocephalus[ 34 ],however, the therapeutic effect of the V-P shunt, or CSF drainage remains controversial. This study reported that NLR is helpful in predicting short prognosis of patients with TBM; however, it has some limitations. This study was a small sample size, only 16 patients died within 28 days, and might affect the stability of logistic model. Diagnosis depended mainly on clinical the clinical criteria, CSF criteria, cerebral imaging criteria, which may bias the data. All patients received antituberculosis treatment, However, patients who stopped treatment due to side effects from the use of antituberculosis drugs were not excluded from the study, which may also affect the results. Some larger sample size studies are needed to validate the effect of NLR values on the short outcome of patients with TBM. Conclusions NLR, peripheral neurological deficit and hydrocephalus were independent predictors of short prognosis and NLR was significantly positively correlated with the severity of TBM. To improve patient outcomes, High NLR values need closer monitoring in patients with TBM. Abbreviations NLR: neutrophil-lymphocyte ratio; CNS: Central nervous system; CSF: Cerebrospinal fluid; TBM: Tuberculous meningitis; OR=odds ratio; CI= confidence interval. Declarations Acknowledgements We acknowledge all the participants for their cooperation. Funding No specific funding was available for this study. Availability of data and materials All data generated or analyzed during this study are included in this published article. Authors’ contributions ZG conceived the study, drafted the manuscript, analyzed the data and critically revised the manuscript for important intellectual content; BL analyzed of the data; XY, TC, TH and LT were involved in the diagnosis and confirmation of tuberculous meningitis patient. Corresponding author was responsible for study concept design; analysis, interpretation and integrity of the data, preparation of the manuscript and reviewed the manuscript for intellectual content. All authors read and approved the final manuscript. Ethics approval and consent to participate The study was approved by the Human Ethics Committee of West China Hospital of Sichuan University (ethics No.: 2018-598) and was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all subjects and/or their legal guardian(s).All methods were performed in accordance with the relevant guidelines and regulations. Conflicts of interest. The authors have no conflicts of interest to declare. Consent for publication Not applicable. References Organization, W.H., Global tuberculosis report 2018 . 2018, World Heath Organization Genebra. Modi, M., et al., Clinical and radiological predictors of outcome in tubercular meningitis: A prospective study of 209 patients. Clin Neurol Neurosurg, 2017. 161 : p. 29-34. Hsu, P.C., et al., Prognostic factors of tuberculous meningitis in adults: a 6-year retrospective study at a tertiary hospital in northern Taiwan. J Microbiol Immunol Infect, 2010. 43 (2): p. 111-8. 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Tables Table 1 the patient’s characteristics with TBM. variable Survival(n = 215) Death(n = 16) p Demographic data sex 0.550 Male, n, % 120(54.8%) 10(62.5%) Female, n, % 99(45.2%) 6(37.5%) Age, years, mean ± SD 37 ± 167 34 ± 16 0.592 Disease duration, day, median,Interquartile range 25%,75%) 29(14, 60) 25(12, 32) 0.536 HIV infection, n, (%) 4 0 1 Clinical criteria Fever(> 37.5℃) > 5days, n,(%) 181(82.6%) 11(68.8%) 0.165 Night sweats, n, (%) 53(24.2%) 2(12.5%) 0.372 Weight loss n, (%) 76(34.9%) 4(25%) 0.587 Cough, n, (%) 46(21.0%) 5(31.3%) 0.337 Headache, n, (%) 201(91.8%) 13(81.3%) 0.161 Vomiting, n, (%) 141(64.4%) 9(56.3%) 0.513 Peripheral neurological deficit, n, (%) 57(26.0%) 12(75.0%) 0.000 Cognitive impairment, n, (%) 38(17.4%) 5(31.3%) 0.165 change of consciousness, n, (%) 93(42.5%) 13(81.3%) 0.003 Cranial nerve palsy, n, (%) 51(23.3%) 6(37.5%) 0.200 seizures, n, (%) 36(16.4%) 5(31.1%) 0.132 Laboratory data Red blood cell,10^12/L, mean ± S 4.43 ± 0.58 4.51 ± 0.65 0.611 Platelet 10^9/L, mean ± S 240 ± 102 225 ± 67 0.563 white blood cell,10^9/L, mean ± S 7.80 ± 3.23 9.54 ± 5.53 0.52 Neutrophil, 10^9/L, mean ± S 6.02 ± 3.18 7.86 ± 5.08 0.172 Lymphocyte, 10^9/L, mean ± S 1.16 ± 0.71 0.87 ± 0.64 0.122 the neutrophil lymphocyte ratio(NLR),% 7.13 ± 6.23 12.51 ± 9.22 0.002 Serum sodium, mmol/L, mean ± SD 132.±7.77 135.02 ± 5.46 0.132 Serum potassium, mmol/L, mean ± SD 3.70 ± 0.47 3.56 ± 0.48 0.241 Plasma glucose, mmol/L, mean ± SD 6.06 ± 1.47 6.41 ± 1.22 0.360 Albumin, g/L, mean ± SD 38.46 ± 4.85 35.93 ± 6.50 0.50 CSF leukocyte count, cell/ul,Interquartile range 25%,75%) 120(60, 270) 125(42.5, 350) 0.936 CSF protein, g/L, median,Interquartile range 25%,75%) 1.57(1.08, 2.54) 2.29(1.17, 4.90) 0.110 CSF chlorine, mmol/L, mean ± SD 114.19 ± 8.32 111.83 ± 9.74 0.280 CSF glucose, mmol/L, mean ± SD 2.05 ± 0.99 2.06 ± 1.40 0.953 Ratio of CSF to blood glucose, mean ± SD 0.355 ± 0.182 0.336 ± 0.234 0.691 Cerebral imaging criteria Hydrocephalus,, n, (%) 60(27.4%) 14(87.5%) 0.000 infarct, n, (%) 87(39.7%) 9(56.3%) 0.201 basal meningeal enhancement, n, (%) 71(32.4%) 7(43.8%) 0.353 tuberculoma, n, (%) 6(2.7%) 1(6.3%) 0.394 Table 2 multivariate analysis of 28-day mortality in patients with TBM Variable OR 95%CI P The neutrophil lymphocyte ratio(NLR) 1.066 1.002, 1.133 0.043 Peripheral neurological deficit 7.485 2.010, 27.876 0.003 Hydrocephalus 11.329 2.395, 53.583 0.002 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Jul, 2023 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Major revision 21 Nov, 2022 Reviewers agreed at journal 07 Nov, 2022 Reviews received at journal 18 Oct, 2022 Reviewers agreed at journal 01 Oct, 2022 Reviewers invited by journal 25 Sep, 2022 Editor assigned by journal 17 Sep, 2022 Editor invited by journal 17 Sep, 2022 Submission checks completed at journal 17 Sep, 2022 First submitted to journal 07 Sep, 2022 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. We do this by developing innovative software and high quality services for the global research community. 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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-2042550","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":137414143,"identity":"8bb1c529-22c6-4a3e-9a65-baec2225935f","order_by":0,"name":"Zhihan Gu","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhihan","middleName":"","lastName":"Gu","suffix":""},{"id":137414144,"identity":"48bc4752-0c26-453d-aa60-0a4b22bf4df3","order_by":1,"name":"Bofu Liu","email":"","orcid":"","institution":"Sichuan 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University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tianyong","middleName":"","lastName":"Han","suffix":""},{"id":137414148,"identity":"b53843d2-7509-4be9-b894-7673093af7ae","order_by":5,"name":"Le Tong","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Le","middleName":"","lastName":"Tong","suffix":""},{"id":137414149,"identity":"cbf43970-921c-4591-aa42-f4e3d90db049","order_by":6,"name":"Yu Cao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApUlEQVRIiWNgGAWjYPACGx5+9gbStKTJSPYcIE3LYRuDGw5EqjW4kWMm8XHPeR6GGwyMHz7mEKlFcsaz2zyMsxuYJWduI1KLNM+B2zzMMgfYmHmJ1vLnwDkeNokEUrQwHDjAw0O0Fskzz4otew4k80jwHGwmzi98x5M33vhxwM7e/njzwQ8fidGicIDDAMpkbCBCPRDIN7A/IE7lKBgFo2AUjFwAAH/bNo0mJvk1AAAAAElFTkSuQmCC","orcid":"","institution":"Sichuan University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Cao","suffix":""}],"badges":[],"createdAt":"2022-09-07 17:29:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2042550/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2042550/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-023-08438-y","type":"published","date":"2023-07-05T21:30:44+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":26738211,"identity":"536106c4-6b61-4de8-bac3-e9683d0386d4","added_by":"auto","created_at":"2022-09-20 23:19:32","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":110520,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution map of the severity of TBM\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2042550/v1/a1cbbf47b967791bdf7baa0e.jpg"},{"id":26738213,"identity":"7b6c8189-d740-4170-8113-b0f10a438416","added_by":"auto","created_at":"2022-09-20 23:19:33","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":152056,"visible":true,"origin":"","legend":"\u003cp\u003eThe ROC curves predicting 28-day mortality for patients with TBM of the NLR\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2042550/v1/414382b261654d580b4afb4c.jpg"},{"id":26738212,"identity":"38f5fe1c-2b8f-46d7-8663-65c84e5e2182","added_by":"auto","created_at":"2022-09-20 23:19:32","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":133671,"visible":true,"origin":"","legend":"\u003cp\u003eMean value of neutrophil lymphocyte ratio of the severity of TBM\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2042550/v1/c1cd9513c3ef3577857f1164.jpg"},{"id":44734084,"identity":"9a03c1a8-1979-49bc-96d7-7228f8932068","added_by":"auto","created_at":"2023-10-16 22:14:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":377636,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2042550/v1/5b9154e6-2578-41eb-af4f-10142ec17403.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"High blood neutrophil-lymphocyte ratio associated with short poor outcome in tuberculous meningitis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTuberculosis (TB) is the major cause of death by an infectious disease around the global[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e],but tuberculous meningitis (TBM) is the most devastating manifestation of infection with mycobacterium tuberculosis[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]. TBM is a kind of inflammation caused by Mycobacterium tuberculosis invading the human central nervous system (including the spinal cord or meninges or brain parenchyma) and then form a series of secondary pathophysiological change in patients\u0026rsquo; brain[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e].The clinical course of TBM is nonspecific and quite variable, it is difficult to predict a prognosis early in the disease. But early identification of high-risk patients with poor prognosis and intensive treatment may improve prognosis of TBM[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. So, early assessment of the risk factor in patients with TBM is crucial in making clinical decisions.\u003c/p\u003e\n\u003cp\u003eEven given anti-tuberculosis treatment, The mortality rate of TBM patients as high as 10\u0026ndash;50%[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]. Some studies indicated that factors such as disturbance of consciousness and hydrocephalus might be correlated with poor outcome for patients with TBM [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, the marker of inflammation in the blood has not be reported about the short prognosis of TBM patients.\u003c/p\u003e\n\u003cp\u003eNeutrophil-lymphocyte ratio (NLR) is defined as the number of neutrophils in whole blood divided by the number of lymphocytes in whole blood[\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e],it is a biomarker derived from leukocytes as a marker of inflammation. The NLR describes is a reliable parameter to describe the immune response to various stimuli/stressors[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e] and has been found to be a useful biomarker for predicting mortality in various clinical setting including sepsis, miliary tuberculosis and bacterial meningitis [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e],but the association of NLR with clinical outcome in patients with TBM has not been reported, This study is expected to explain the role of NLR as a predictor of short prognosis in patients with TBM.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003ePatients and diagnosis of TBM\u003c/h2\u003e\n\u003cp\u003eWe retrospectively collected the data of all patients (\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;15year-old) who were admitted to the West China Hospital, Sichuan University and diagnosed with TBM, from the period bet\u003cem\u003ew\u003c/em\u003eeen January 1st, 2018 and August 1st, 2019. Patients were eligible for inclusion according to the standardized case definition of TBM proposed by Marais including the clinical criteria, CSF criteria, cerebral imaging criteria, evidence of tuberculosis elsewhere and exclusion of alternative diagnoses: An alternative diagnosis must be confirmed microbiologically, serologically, or histopathologically[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. Patients with data was insufficient and pregnant was excluded from the study.\u003c/p\u003e\n\u003ch2\u003eCollection of clinical data\u003c/h2\u003e\n\u003cp\u003eThe data information of patients was obtained by the patients\u0026rsquo; electronic medical record management system and telephone. The data included Demographic data(gender, age, duration of illness, HIV-infected), the clinical criteria (fever(\u0026gt;\u0026thinsp;37.5℃)\u0026thinsp;\u0026gt;\u0026thinsp;5days, night sweats, weight loss, cough, headache, vomiting, peripheral nerve dysfunction, cognitive impairment, change of consciousness, cranial nerve paralysis, seizures), laboratory data (red blood cell counts, white blood cell counts, platelet, plasma sodium, plasma potassium, plasma glucose, albumin ,CSF cells, CSF protein, CSF glucose, CSF to plasma glucose ratio, CSF chlorine)and cerebral imaging criteria (Hydrocephalus、Basal meningeal enhancement、Tuberculoma、Infarct)were collected based on the first available data at the time of admission and included complete blood cell counts .We also collected the outcome (survivors and non-survivors) after 28 day and the severity of TBM at the time of admission which was assessed using the British Medical Research Council (BMRC) TBM stages. this was modified as grade I (GCS 15; no focal neurological signs), grade II (GCS 11\u0026ndash;14, or 15 with focal neurological signs), and grade III (GCS\u0026thinsp;\u0026le;\u0026thinsp;10) disease.[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\n\u003ch2\u003eManagement\u003c/h2\u003e\n\u003cp\u003ePatients received four TBM treatments, isoniazid (10\u0026ndash;20 mg/day; maximum 1200 mg/day), rifampicin (10\u0026ndash;20 mg/day; maximum 600 mg/day), pyrazinamide (20\u0026ndash;30 mg/day; maximum 1500 mg/ day), and ethambutol: (15\u0026ndash;20 mg/day; maximum 750 mg/day), they also received dexamethasone during early treatment.\u003c/p\u003e\n\u003cdiv class=\"Section2\" id=\"Sec2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003eA chi-squared or Fisher\u0026rsquo;s exact test was implemented to compare the categorical variables. An independent-sample test was utilized to compare the continuous variables. Multivariable analysis was executed by the logistic regression model to verify the independence of the 28-day mortality, and the Lemeshow-Hosmer \u0026chi;2 statistics was used to evaluate the Goodness-of-fit of the model. Discrimination power of for predicting 28-day mortality was assessed via Receiver Operating Characteristic (ROC) curve. Spearman correlation analysis was performed to discuss correlation about and the severity of TBM. All statistical analyses were implemented with the use of SPSS software version 22.0 (USA, IBM analytics). A P value equal or less than 0.05 was statistically significant in all analyses.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThere were 245 patients with TBM who were treated at the West China Hospital, Sichuan University. 14 patients were excluded from the study, among them, 10 patients had insufficient data and 4 patients were pregnant, finally, a total of 231 patients were analyzed in this study. there were 16 (6.95) patients who died in this study period and the remaining 215(93.1%) patients survived.\u003c/p\u003e\n\u003cp\u003eIn the study, there are 130 (56.3%) men and 105 (43.7%) women. The mean age was 36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7years (range 15\u0026ndash;78years),4 patients are HIV-infected who are survivors, The patients were divided into three stages according to the severity: 68 (29.4%) patients were classified as stage I; 142(61.5%) patients were stage II, among them;25(10.8%) patients were stage III(Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e describes the patients' characteristics between the between survivors and non-survivors.\u003c/p\u003e\n\u003cp\u003eNLR was higher in the non-survivors compared with survivors (P\u0026thinsp;=\u0026thinsp;0.002), but albumin was lower in the non-survivors(P\u0026thinsp;=\u0026thinsp;0.05). TBM patients with survivors had more Peripheral neurological deficit (P＜0.001), loss of consciousness (P\u0026thinsp;=\u0026thinsp;0.003), and hydrocephalus(P＜0.001) than non-survivors patients. There was no significant statistical difference in the other factors.\u003c/p\u003e\n\u003cp\u003eMultivariate logistic regression models (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e) indicated that the NLR was associated with the independent risks of 28-day mortality(OR\u0026thinsp;=\u0026thinsp;1.066, 95% CI\u0026thinsp;=\u0026thinsp;1.002\u0026ndash;1.133, p\u0026thinsp;=\u0026thinsp;0.043), meanwhile, the non-survivors patients were significantly more likely to have peripheral neurological deficit (OR 7.485, 95% CI2.010-27.876, P\u0026thinsp;=\u0026thinsp;0 .003)and hydrocephalus (OR 11.329, 95% CI 2.395\u0026ndash;53.583, P\u0026thinsp;=\u0026thinsp;0 .002)than survivors patients. There were no differences in the rate of loss of consciousness and in the level of albumin. The Hosmer-Lemeshow\u0026chi;2 statistics of the univariate logistic regression models was1.260 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.996).\u003c/p\u003e\n\u003cp\u003eThe area under the curve (AUC) of the ROC curves predicting 28-day mortality for patients with TBM of the NLR was 0.687 (95% CI 0.546\u0026ndash;0.828, p\u0026thinsp;=\u0026thinsp;0.013), the optimal cut off result is 5.225. By using a cutoff point of 9.9904, the NLR has a sensitivity of 56.3% and a specificity of 81.3% (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe Study explored the relationship between the severity of TBM and the NLR. The NLR was 6.00\u0026thinsp;\u0026plusmn;\u0026thinsp;5.03 when the patients were in stage I, the NLR was 7.43\u0026thinsp;\u0026plusmn;\u0026thinsp;6.92when the patients were in stage II, the NLR was 12.00\u0026thinsp;\u0026plusmn;\u0026thinsp;9.92when the patients were in stage III(Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Spearman correlation analysis showed the severity of TBM was significantly positively correlated with the NLR (r\u0026thinsp;=\u0026thinsp;0.216, p\u0026thinsp;=\u0026thinsp;0.01).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIN the study, NLR is an independent predictor for short prognosis in patients with TBM. NLR is an inflammatory marker that can be obtained simply and fast. NLR represents the relative neutrophil elevation or lymphocyte decrease. A number of studies have reported that high NLR is associated with high mortality in cancers[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] or cardiovascular diseases[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In this study, association of high NLR with high severity of TBM is also represented as some study has reported that high NLR may have a higher cancer stage[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] or the severity of pulmonary TB[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. At present, the cause for the correlation between the increase in NLR and poor outcome has not yet been explained clearly. High neutrophil counts or lymphopenia may be associated with poor prognosis in several previous studies on TB[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], but NLR has not been represented in the patients with TBM. Chedid, C hypothesized that high neutrophil counts and low lymphocyte proportions had highly inflammatory clinical patterns by the context of mycobacterial infection[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], which are markers of persisting inflammation or failure to clear the bacteria [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. High neutrophil counts may reflect the presence of delayed apoptosis in inflammatory condition, and inhibit the anti-inflammatory ability of neutrophil cells[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In chronic TB infection, sustained inflammation which was an impairment maker of the TB-specific immune response and a marker of active disease has be reported[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. High NLR may represent relative lymphopenia, low lymphocyte counts are associated with a negative response to treatment[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]in relation to cell-mediated immunity which is important in the immune response to M. tuberculosis[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. So, the similar pathway may have affected the progression and prognosis of TBM.\u003c/p\u003e \u003cp\u003eIn this study, peripheral neurological deficit is a predictor of poor outcome in patients with TBM. A series of studies had reported similar conclusion [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. About 15\u0026ndash;50% of patients with TBM have exist peripheral neurological deficit when they first present symptom[\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e],this study reported 30% (69/231) of patients with TBM. This condition may be associated with high rates of morbidity and mortality. Some studies also reported cranial nerve palsy is a risk factors association with bad outcome[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e],but this study did not support it. this study focused the 28-day mortality however those studies had a long-term follow-up result.\u003c/p\u003e \u003cp\u003eHydrocephalus is a quite common complication of TBM, as reported, up to 60% of patients with TBM be found to by cranial imaging such as MRI/CT[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. hydrocephalus of TBM may be associated a pathogenesis of meningeal exudate and either overproduction of CSF or malfunctioning absorption of CSF in the subarachnoid space[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e],and is thought to be an important risk factor of poor outcome. the V-P shunt, or CSF drainage is a management way of hydrocephalus[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e],however, the therapeutic effect of the V-P shunt, or CSF drainage remains controversial.\u003c/p\u003e \u003cp\u003eThis study reported that NLR is helpful in predicting short prognosis of patients with TBM; however, it has some limitations. This study was a small sample size, only 16 patients died within 28 days, and might affect the stability of logistic model. Diagnosis depended mainly on clinical the clinical criteria, CSF criteria, cerebral imaging criteria, which may bias the data. All patients received antituberculosis treatment, However, patients who stopped treatment due to side effects from the use of antituberculosis drugs were not excluded from the study, which may also affect the results. Some larger sample size studies are needed to validate the effect of NLR values on the short outcome of patients with TBM.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eNLR, peripheral neurological deficit and hydrocephalus were independent predictors of short prognosis and NLR was significantly positively correlated with the severity of TBM. To improve patient outcomes, High NLR values need closer monitoring in patients with TBM.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNLR: neutrophil-lymphocyte ratio; CNS: Central nervous system; CSF: Cerebrospinal fluid; TBM: Tuberculous meningitis; OR=odds ratio; CI= confidence interval.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eWe acknowledge all the participants for their cooperation.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNo specific funding was available for this study.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eZG conceived the study, drafted the manuscript, analyzed the data and critically revised the manuscript for important intellectual content; BL analyzed of the data; XY, TC, TH and LT were involved in the diagnosis and confirmation of tuberculous meningitis patient. Corresponding author was responsible for study concept design; analysis, interpretation and integrity of the data, preparation of the manuscript and reviewed the manuscript for intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Human Ethics Committee of West China Hospital of Sichuan University (ethics No.: 2018-598) and was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all subjects and/or their legal guardian(s).All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003eConflicts of interest.\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOrganization, W.H., \u003cem\u003eGlobal tuberculosis report 2018\u003c/em\u003e. 2018, World Heath Organization Genebra.\u003c/li\u003e\n\u003cli\u003eModi, M., et al., \u003cem\u003eClinical and radiological predictors of outcome in tubercular meningitis: A prospective study of 209 patients.\u003c/em\u003e Clin Neurol Neurosurg, 2017. \u003cstrong\u003e161\u003c/strong\u003e: p. 29-34.\u003c/li\u003e\n\u003cli\u003eHsu, P.C., et al., \u003cem\u003ePrognostic factors of tuberculous meningitis in adults: a 6-year retrospective study at a tertiary hospital in northern Taiwan.\u003c/em\u003e J Microbiol Immunol Infect, 2010. \u003cstrong\u003e43\u003c/strong\u003e(2): p. 111-8.\u003c/li\u003e\n\u003cli\u003eCrevel, R.v., R. Ruslami, and R. Aarnoutse, \u003cem\u003eTherapy for tuberculous meningitis.\u003c/em\u003e 2016.\u003c/li\u003e\n\u003cli\u003eChou, C.H., et al., \u003cem\u003eComparison of the APACHE II, GCS and MRC scores in predicting outcomes in patients with tuberculous meningitis.\u003c/em\u003e Int J Tuberc Lung Dis, 2010. \u003cstrong\u003e14\u003c/strong\u003e(1): p. 86-92.\u003c/li\u003e\n\u003cli\u003eVan, T.T. and J. Farrar, \u003cem\u003eTuberculous meningitis.\u003c/em\u003e J Epidemiol Community Health, 2014. \u003cstrong\u003e68\u003c/strong\u003e(3): p. 195-6.\u003c/li\u003e\n\u003cli\u003eImtiaz, F., et al., \u003cem\u003eNeutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population.\u003c/em\u003e International archives of medicine, 2012. \u003cstrong\u003e5\u003c/strong\u003e(1): p. 1-6.\u003c/li\u003e\n\u003cli\u003eZhou, T., et al., \u003cem\u003ePrognostic value of neutrophil-lymphocyte count ratio (NLCR) among adult ICU patients in comparison to APACHE II score and conventional inflammatory markers: a multi center retrospective cohort study.\u003c/em\u003e BMC emergency medicine, 2021. \u003cstrong\u003e21\u003c/strong\u003e(1): p. 1-10.\u003c/li\u003e\n\u003cli\u003eHan, Y., et al., \u003cem\u003eHigh blood neutrophil-lymphocyte ratio associated with poor outcomes in miliary tuberculosis.\u003c/em\u003e Journal of thoracic disease, 2018. \u003cstrong\u003e10\u003c/strong\u003e(1): p. 339.\u003c/li\u003e\n\u003cli\u003eWidjaja, H., et al., \u003cem\u003eNeutrophil lymphocyte ratio as predictor of mortality in pediatric patients with bacterial meningitis: A retrospective cohort study.\u003c/em\u003e Annals of Medicine and Surgery, 2022. \u003cstrong\u003e73\u003c/strong\u003e: p. 103191.\u003c/li\u003e\n\u003cli\u003eMarais, S., et al., \u003cem\u003eTuberculous meningitis: a uniform case definition for use in clinical research.\u003c/em\u003e The Lancet infectious diseases, 2010. \u003cstrong\u003e10\u003c/strong\u003e(11): p. 803-812.\u003c/li\u003e\n\u003cli\u003eCupp, M.A., et al., \u003cem\u003eNeutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies.\u003c/em\u003e BMC medicine, 2020. \u003cstrong\u003e18\u003c/strong\u003e(1): p. 1-16.\u003c/li\u003e\n\u003cli\u003eMarchetti, C., et al., \u003cem\u003eNLR and BRCA mutational status in patients with high grade serous advanced ovarian cancer.\u003c/em\u003e Scientific Reports, 2021. \u003cstrong\u003e11\u003c/strong\u003e(1): p. 1-8.\u003c/li\u003e\n\u003cli\u003eAyers, K.L., et al., \u003cem\u003eA composite biomarker of neutrophil-lymphocyte ratio and hemoglobin level correlates with clinical response to PD-1 and PD-L1 inhibitors in advanced non-small cell lung cancers.\u003c/em\u003e BMC cancer, 2021. \u003cstrong\u003e21\u003c/strong\u003e(1): p. 1-11.\u003c/li\u003e\n\u003cli\u003ePapa, A., et al., \u003cem\u003ePredictive value of elevated neutrophil\u0026ndash;lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease.\u003c/em\u003e Clinica chimica acta, 2008. \u003cstrong\u003e395\u003c/strong\u003e(1-2): p. 27-31.\u003c/li\u003e\n\u003cli\u003eAdamstein, N.H., et al., \u003cem\u003eThe neutrophil\u0026ndash;lymphocyte ratio and incident atherosclerotic events: analyses from five contemporary randomized trials.\u003c/em\u003e European heart journal, 2021. \u003cstrong\u003e42\u003c/strong\u003e(9): p. 896-903.\u003c/li\u003e\n\u003cli\u003eTempleton, A.J., et al., \u003cem\u003ePrognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis.\u003c/em\u003e JNCI: Journal of the National Cancer Institute, 2014. \u003cstrong\u003e106\u003c/strong\u003e(6).\u003c/li\u003e\n\u003cli\u003eNaghavi, M., et al., \u003cem\u003eGlobal, regional, and national age-sex specific mortality for 264 causes of death, 1980\u0026ndash;2016: a systematic analysis for the Global Burden of Disease Study 2016.\u003c/em\u003e The lancet, 2017. \u003cstrong\u003e390\u003c/strong\u003e(10100): p. 1151-1210.\u003c/li\u003e\n\u003cli\u003eAbakay, O., et al., \u003cem\u003eThe relationship between inflammatory marker levels and pulmonary tuberculosis severity.\u003c/em\u003e Inflammation, 2015. \u003cstrong\u003e38\u003c/strong\u003e(2): p. 691-696.\u003c/li\u003e\n\u003cli\u003eChedid, C., et al., \u003cem\u003eAssociation of baseline white blood cell counts with tuberculosis treatment outcome: a prospective multicentered cohort study.\u003c/em\u003e International Journal of Infectious Diseases, 2020. \u003cstrong\u003e100\u003c/strong\u003e: p. 199-206.\u003c/li\u003e\n\u003cli\u003eOkamura, K., et al., \u003cem\u003eHypoalbuminemia and lymphocytopenia are predictive risk factors for in-hospital mortality in patients with tuberculosis.\u003c/em\u003e Internal medicine, 2013. \u003cstrong\u003e52\u003c/strong\u003e(4): p. 439-444.\u003c/li\u003e\n\u003cli\u003eSrivastava, S., J.D. Ernst, and L. Desvignes, \u003cem\u003eBeyond macrophages: the diversity of mononuclear cells in tuberculosis.\u003c/em\u003e Immunological reviews, 2014. \u003cstrong\u003e262\u003c/strong\u003e(1): p. 179-192.\u003c/li\u003e\n\u003cli\u003eZahorec, R., \u003cem\u003eRatio of neutrophil to lymphocyte counts-rapid and simple parameter of systemic inflammation and stress in critically ill.\u003c/em\u003e Bratislavske lekarske listy, 2001. \u003cstrong\u003e102\u003c/strong\u003e(1): p. 5-14.\u003c/li\u003e\n\u003cli\u003eSia, J.K. and J. Rengarajan, \u003cem\u003eImmunology of Mycobacterium tuberculosis infections.\u003c/em\u003e Microbiology spectrum, 2019. \u003cstrong\u003e7\u003c/strong\u003e(4): p. 7.4. 6.\u003c/li\u003e\n\u003cli\u003eYin, Y., et al., \u003cem\u003ePretreatment neutrophil-to-lymphocyte ratio in peripheral blood was associated with pulmonary tuberculosis retreatment.\u003c/em\u003e Archives of Medical Science, 2017. \u003cstrong\u003e13\u003c/strong\u003e(2): p. 404-411.\u003c/li\u003e\n\u003cli\u003eCherian, A. and S. Thomas, \u003cem\u003eCentral nervous system tuberculosis.\u003c/em\u003e African health sciences, 2011. \u003cstrong\u003e11\u003c/strong\u003e(1).\u003c/li\u003e\n\u003cli\u003eMisra, U., et al., \u003cem\u003eRole of clinical, radiological, and neurophysiological changes in predicting the outcome of tuberculous meningitis: a multivariable analysis.\u003c/em\u003e Journal of Neurology, Neurosurgery \u0026amp; Psychiatry, 2000. \u003cstrong\u003e68\u003c/strong\u003e(3): p. 300-303.\u003c/li\u003e\n\u003cli\u003eKalita, J., U.K. Misra, and P. Ranjan, \u003cem\u003ePredictors of long-term neurological sequelae of tuberculous meningitis: a multivariate analysis.\u003c/em\u003e Eur J Neurol, 2007. \u003cstrong\u003e14\u003c/strong\u003e(1): p. 33-7.\u003c/li\u003e\n\u003cli\u003ePehlivanoglu, F., K. Kart Yasar, and G. Sengoz, \u003cem\u003eTuberculous meningitis in adults: a review of 160 cases.\u003c/em\u003e The Scientific World Journal, 2012. \u003cstrong\u003e2012\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eLi, K., et al., \u003cem\u003eClinical features, long-term clinical outcomes, and prognostic factors of tuberculous meningitis in West China: a multivariate analysis of 154 adults.\u003c/em\u003e Expert Rev Anti Infect Ther, 2017. \u003cstrong\u003e15\u003c/strong\u003e(6): p. 629-635.\u003c/li\u003e\n\u003cli\u003eSharma, P., et al., \u003cem\u003eIncidence, predictors and prognostic value of cranial nerve involvement in patients with tuberculous meningitis: a retrospective evaluation.\u003c/em\u003e Eur J Intern Med, 2011. \u003cstrong\u003e22\u003c/strong\u003e(3): p. 289-95.\u003c/li\u003e\n\u003cli\u003eFeng, B., et al., \u003cem\u003ePrognostic factors of adult tuberculous meningitis in intensive care unit: a single-center retrospective study in East China.\u003c/em\u003e BMC neurology, 2021. \u003cstrong\u003e21\u003c/strong\u003e(1): p. 1-11.\u003c/li\u003e\n\u003cli\u003eSheu, J.J., et al., \u003cem\u003eClinical characteristics and treatment delay of cerebral infarction in tuberculous meningitis.\u003c/em\u003e Intern Med J, 2012. \u003cstrong\u003e42\u003c/strong\u003e(3): p. 294-300.\u003c/li\u003e\n\u003cli\u003eHuang, H.J., et al., \u003cem\u003eOld age and hydrocephalus are associated with poor prognosis in patients with tuberculous meningitis: A retrospective study in a Chinese adult population.\u003c/em\u003e Medicine (Baltimore), 2017. \u003cstrong\u003e96\u003c/strong\u003e(26): p. e7370.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ethe patient\u0026rsquo;s characteristics with TBM.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003evariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSurvival(n\u0026thinsp;=\u0026thinsp;215)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDeath(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDemographic data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.550\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale, n, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120(54.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(62.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale, n, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99(45.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, years, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u0026thinsp;\u0026plusmn;\u0026thinsp;167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.592\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease duration, day, median,Interquartile range 25%,75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29(14, 60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25(12, 32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.536\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHIV infection, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinical criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFever(\u0026gt;\u0026thinsp;37.5℃)\u0026thinsp;\u0026gt;\u0026thinsp;5days, n,(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e181(82.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(68.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNight sweats, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53(24.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.372\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight loss n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76(34.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.587\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCough, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46(21.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(31.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeadache, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e201(91.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(81.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVomiting, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e141(64.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(56.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.513\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeripheral neurological deficit, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57(26.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCognitive impairment, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38(17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(31.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003echange of consciousness, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93(42.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(81.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCranial nerve palsy, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51(23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eseizures, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(16.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(31.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLaboratory data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRed blood cell,10^12/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.611\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlatelet 10^9/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e240\u0026thinsp;\u0026plusmn;\u0026thinsp;102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e225\u0026thinsp;\u0026plusmn;\u0026thinsp;67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.563\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ewhite blood cell,10^9/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.80\u0026thinsp;\u0026plusmn;\u0026thinsp;3.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.54\u0026thinsp;\u0026plusmn;\u0026thinsp;5.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeutrophil, 10^9/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.86\u0026thinsp;\u0026plusmn;\u0026thinsp;5.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.172\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymphocyte, 10^9/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ethe neutrophil lymphocyte ratio(NLR),%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.13\u0026thinsp;\u0026plusmn;\u0026thinsp;6.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.51\u0026thinsp;\u0026plusmn;\u0026thinsp;9.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSerum sodium, mmol/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e132.\u0026plusmn;7.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e135.02\u0026thinsp;\u0026plusmn;\u0026thinsp;5.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSerum potassium, mmol/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.241\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlasma glucose, mmol/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.360\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin, g/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.46\u0026thinsp;\u0026plusmn;\u0026thinsp;4.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.93\u0026thinsp;\u0026plusmn;\u0026thinsp;6.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF leukocyte count, cell/ul,Interquartile range 25%,75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120(60, 270)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e125(42.5, 350)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.936\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF protein, g/L, median,Interquartile range 25%,75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.57(1.08, 2.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.29(1.17, 4.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF chlorine, mmol/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e114.19\u0026thinsp;\u0026plusmn;\u0026thinsp;8.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111.83\u0026thinsp;\u0026plusmn;\u0026thinsp;9.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF glucose, mmol/L, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.953\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRatio of CSF to blood glucose, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.355\u0026thinsp;\u0026plusmn;\u0026thinsp;0.182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.336\u0026thinsp;\u0026plusmn;\u0026thinsp;0.234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.691\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCerebral imaging criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHydrocephalus,, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60(27.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einfarct, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87(39.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(56.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ebasal meningeal enhancement, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71(32.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(43.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.353\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003etuberculoma, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003emultivariate analysis of 28-day mortality in patients with TBM\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThe neutrophil lymphocyte ratio(NLR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.002, 1.133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeripheral neurological deficit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.485\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.010, 27.876\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHydrocephalus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.329\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.395, 53.583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\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-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Tuberculous meningitis, neutrophil-lymphocyte ratio(NLR), prognosis","lastPublishedDoi":"10.21203/rs.3.rs-2042550/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2042550/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIt is difficult to predict the short prognosis of tuberculous meningitis (TBM), no study reported the neutrophil lymphocyte ratio(NLR) as a predictor of short prognosis in TBM and the relationship between NLR and the severity of TBM. We hypothesized that NLR is an indicator to reflect independent prognostic significance in patients with TBM and there is a correlation between NLR and the severity of TBM. This study aimed to know the role of the neutrophil lymphocyte ratio as a predictor of 28-mortality and the relationship with the severity of TBM in patients with TBM.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively collected data from patients diagnosed with TBM in the West China Hospital, Sichuan University, from the period bet\u003cem\u003ew\u003c/em\u003eeen January 1st, 2018 and August 1st, 2019. Multivariable analysis was executed by the logistic regression model to verify the independence of the 28-day mortality, Spearman correlation analysis was performed to discuss correlation about and the severity of TBM.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 231 patients were enrolled. 68 (29.4%) patients were classified as stage I. 142(61.5%) patients were stage II.25(10.8) patients were stage III. 16(6.9%) patients died during the follow-up period of 28 days. By multiple logistic regression analyses, the NLR(OR\u0026thinsp;=\u0026thinsp;1.066, 95% CI\u0026thinsp;=\u0026thinsp;1.002\u0026ndash;1.133, p\u0026thinsp;=\u0026thinsp;0.043), peripheral neurological deficit (OR 7.485, 95% CI2.010-27.876, P\u0026thinsp;=\u0026thinsp;0 .003)and hydrocephalus (OR 11.329, 95% CI 2.395\u0026ndash;53.583, P\u0026thinsp;=\u0026thinsp;0 .002) were associated with the independent risks of 28-day mortality. Spearman correlation analysis showed the severity of TBM was significantly positively correlated with the NLR(r\u0026thinsp;=\u0026thinsp;0.216, p\u0026thinsp;=\u0026thinsp;0.01).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eNLR, peripheral neurological deficit and hydrocephalus were independent predictors of short prognosis and NLR was significantly positively correlated with the severity of TBM.\u003c/p\u003e","manuscriptTitle":"High blood neutrophil-lymphocyte ratio associated with short poor outcome in tuberculous meningitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-20 23:19:31","doi":"10.21203/rs.3.rs-2042550/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-11-21T10:13:08+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"7070f979-b608-4f61-a294-80c63134e2ff","date":"2022-11-08T00:07:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-10-18T15:59:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8ce116ce-09de-464e-9627-e58ba13c0f7a","date":"2022-10-01T16:26:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-09-25T15:30:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-09-17T12:24:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-09-17T09:23:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-09-17T09:20:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2022-09-07T17:21:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f6f4579b-1ba7-41c7-ae47-cb57da22ccb1","owner":[],"postedDate":"September 20th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T21:55:50+00:00","versionOfRecord":{"articleIdentity":"rs-2042550","link":"https://doi.org/10.1186/s12879-023-08438-y","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2023-07-05 21:30:44","publishedOnDateReadable":"July 5th, 2023"},"versionCreatedAt":"2022-09-20 23:19:31","video":"","vorDoi":"10.1186/s12879-023-08438-y","vorDoiUrl":"https://doi.org/10.1186/s12879-023-08438-y","workflowStages":[]},"version":"v1","identity":"rs-2042550","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2042550","identity":"rs-2042550","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}