Neutrophils In Cerebrospinal Fluid Research Articles

Artificial Intelligence in Differential Diagnostics of Meningitis: A Nationwide Study.

Differential diagnosis between bacterial and viral meningitis is crucial. In our study, to differentiate bacterial vs. viral meningitis, three machine learning (ML) algorithms (multiple logistic regression (MLR), random forest (RF), and naïve-Bayes (NB)) were applied for the two age groups (0–14 and >14 years) of patients with meningitis by both conventional (culture) and molecular (PCR) methods. Cerebrospinal fluid (CSF) neutrophils, CSF lymphocytes, neutrophil-to-lymphocyte ratio (NLR), blood albumin, blood C-reactive protein (CRP), glucose, blood soluble urokinase-type plasminogen activator receptor (suPAR), and CSF lymphocytes-to-blood CRP ratio (LCR) were used as predictors for the ML algorithms. The performance of the ML algorithms was evaluated through a cross-validation procedure, and optimal predictions of the type of meningitis were above 95% for viral and 78% for bacterial meningitis. Overall, MLR and RF yielded the best performance when using CSF neutrophils, CSF lymphocytes, NLR, albumin, glucose, gender, and CRP. Also, our results reconfirm the high diagnostic accuracy of NLR in the differential diagnosis between bacterial and viral meningitis.

Influence of Strongyloides stercoralis Coinfection on the Presentation, Pathogenesis, and Outcome of Tuberculous Meningitis.

BackgroundHelminth infections may modulate the inflammatory response to Mycobacterium tuberculosis and influence disease presentation and outcome. Strongyloides stercoralis is common among populations with high tuberculosis prevalence. Our aim was to determine whether S. stercoralis coinfection influenced clinical presentation, cerebrospinal fluid (CSF) inflammation, and outcome from tuberculous meningitis (TBM).MethodsFrom June 2017 to December 2019, 668 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817 and NCT03100786), underwent pretreatment S. stercoralis testing by serology, stool microscopy, and/or stool polymerase chain reaction. Comparisons of pretreatment TBM severity, CSF inflammation (including cytokines), and 3-month clinical end points were performed in groups with or without active S. stercoralis infection.ResultsOverall, 9.4% participants (63 of 668) tested positive for S. stercoralis. Active S. stercoralis infection was significantly associated with reduced pretreatment CSF neutrophil counts (median [interquartile range], 3/μL [0–25/μL] vs 14 /μL [1–83/μL]; P = .04), and with reduced CSF interferon ɣ, interleukin 2, and tumor necrosis factor α concentrations (11.4 vs 56.0 pg/mL [P = .01], 33.1 vs 54.5 pg/mL [P = .03], and 4.5 vs 11.9 pg/mL [P = .02], respectively), compared with uninfected participants. Neurological complications by 3 months were significantly reduced in participants with active S. stercoralis infection compared with uninfected participants (3.8% [1 of 26] vs 30.0% [33 of 110], respectively; P = .01).Conclusions S. stercoralis coinfection may modulate the intracerebral inflammatory response to M. tuberculosis and improve TBM clinical outcomes.

Diagnostic Accuracy of Cerebrospinal Fluid Neutrophil Gelatinase-Associated Lipocalin in Patients with Acute Bacterial Meningitis: A Prospective Cohort Study

Background: It is difficult for early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM).Therefore, a novel and reliable biomarker is urgently required. Neutrophil Gelatinase-Associated Lipocalin (NGAL) have been reported as a novel biomarker for differentiating the bacterial or viral infections, however, whether the CSF NGAL is a potential biomarker for distinguishing between BM and TBM or CM are not reported. Methods: Prospectively enrolled the patients with suspected CNS infections at admission, and divided them into three case groups: BM (n=47), TBM (n=34), CM (n=30), and a hospitalized control (HC, n=39). Detected the CSF NGAL and evaluate the diagnostic accuracy to distinguish between BM and TBM or CM. Meanwhile, longitudinally measured the CSF NGAL of BM to evaluate whether it would be a monitor of the antibacterial treatment. Results: The CSF NGAL in BM was significantly higher than TBM, CM and HC, and the serum NGAL was not significantly different among three case groups. The ROC analysis showed that CSF NGAL presented a good diagnostic performance with an AUC of 0.907(95% CI: 0.830 to 0.985), and at the optimal cutoff value of 16.55 ng/mL with 88.46% sensitivity and 81.25% specificity for discriminating BM from TBM or CM. Meanwhile, the CSF NGAL in convalescent period of BM was significantly lower than the acute period. Conclusion: CSF NGAL could be used as an early diagnostic biomarker of BM, especially when compared with TBM or CM, and it also might be have some important clinical value for monitoring antibiotic therapy of BM. Funding Statement: The study was supported in part by the grants from the National Natural Science Foundation of China (No.81802088), the Joint Funds for the innovation of science and Technology, Fujian Province (No.2018Y9080), the Natural Science Foundation of Fujian Province (No.2016J05185), and the Youth Foundation of Health and Family Planning Commission of Fujian Province (No.2016-1-55). Declaration of Interests: The authors: No reported conflicts of interest. Ethics Approval Statement: The study protocol was approved by the Institutional Review Board of the First Affiliated Hospital of Fujian Medical University. Written informed consent was obtained from the participants or their surrogates prior to the study.

A Diagnostic Formula for Discrimination of Tuberculous and Bacterial Meningitis Using Clinical and Laboratory Features

Background: The discrimination of tuberculous meningitis and bacterial meningitis remains difficult at present, even with the introduction of advanced diagnostic tools. This study aims to differentiate these two kinds of meningitis by using the rule of clinical and laboratory features.Methods: A prospective observational study was conducted to collect the clinical and laboratory parameters of patients with tuberculous meningitis or bacterial meningitis. Logistic regression was used to define the diagnostic formula for the discrimination of tuberculous meningitis and bacterial meningitis. A receiver operator characteristic curve was established to determine the best cutoff point for the diagnostic formula.Results: Five parameters (duration of illness, coughing for two or more weeks, meningeal signs, blood sodium, and percentage of neutrophils in cerebrospinal fluid) were predictive of tuberculous meningitis. The diagnostic formula developed from these parameters was 98% sensitive and 82% specific, while these were 95% sensitive and 91% specific when prospectively applied to another 70 patients.Conclusion: The diagnostic formula developed in the present study can help physicians to differentiate tuberculous meningitis from bacterial meningitis in high-tuberculosis-incidence-areas, particularly in settings with limited microbiological and radiological resources.

Clinical application of the detection of heparin-binding protein in cerebrospinal fluid in intracranial infectious diseases

Objective To investigate the clinical application value of the levels of heparin- binding protein (HBP) in cerebrospinal fluid (CSF) for intracranial infectious diseases. Methods A case-control study was conducted. 150 patients after craniotomy(73 in the postoperative bacterial intracranial infection group, 77 in the postoperative non-infection group) admitted to the Department of Neurology of the People′s Hospital of Liaoning Province from December 2016 to May 2018 were collected. At the same time, 46 patients without operation (14 in the non-bacterial intracranial infection group, 32 patients without intracranial infection were selected as control group whose white blood cell count (WBC) values in CSF were all below 10×106/L) in the same period were also collected. According to the diagnostic criteria for severe intracranial infection, the patients with bacterial intracranial infection were divided into 26 cases of mild intracranial infection group and 47 cases of severe intracranial infection group. According to the Glasgow Outcome Scale (GOS) score at the time of discharge, the patients were divided into 30 cases of good prognosis group (GOS score 4-5 points) and 43 cases of poor prognosis group (GOS score 1-3 points). The concentrations of HBP in CSF were tested with latex immunoturbidimetry, and the concentrations of procalcitonin(PCT) in cerebrospinal fluid and serum were tested with electrochemiluminescence, and cerebrospinal fluid routine were tested with instrument method, and the concentrations of total protein(TP) in cerebrospinal fluid were tested with turbidimetry. The differences of the laboratory test indicators in each group were statistically analyzed, and the levels of HBP in CSF of patients with different degrees of intracranial infection and different prognosis were compared. Comparison of two independent samples was performed using the Mann-Whitney U test. Results The HBP levels in cerebrospinal fluid were 187.00 (73.00, 635.00) ng/ml, 10.00 (3.50, 32.00) ng/ml, 1.50 (0, 4.00) ng/ml, 3.00 (1.00, 4.00) ng/ml in post-craniotomy bacterial intracranial infection group, uninfected group after craniotomy, non-bacterial intracranial infection group and control group respectively. The cerebrospinal fluid levels of WBC count were 1 280.00 (363.00, 4 327.00)×106/L, 63.00 (18.50, 300.00)×106/L, 5.00 (3.00, 14.75)×106/L, 3.00 (2.00, 5.75)×106/L. The absolute value of cerebrospinal fluid neutrophils were 1 216.00 (225.50, 3 895.50)×106/L, 24.00 (2.00, 209.50)×106/L, 1.00 (1.00, 3.00)×106/L, 1.00 (1.00, 1.00)×106/L. The cerebrospinal fluid levels of PCT were 0.16 (0.10, 0.32) ng/ml, 0.09 (0.07, 0.14) ng/ml, 0.07 (0.06, 0.12) ng/ml, 0.07 (0.06, 0.13) ng/ml. The serum levels of PCT were 0.36 (0.15, 1.09) ng/ml, 0.09 (0.04, 0.16) ng/ml, 0.08 (0.04, 0.13) ng/ml, 0.07 (0.03, 0.11) ng/ml. The levels of HBP, WBC, neutrophils, PCT in CSF and serum PCT in the post-craniotomy bacterial intracranial infection group were significantly higher than those in the uninfected group after craniotomy (Z=-9.246,-6.759,-6.741,-4.477,-6.202, P 0.05)between the uninfected group after craniotomy and the non-bacterial intracranial infection group. There were significant differences in the levels of HBP, WBC and neutrophils in CSF(Z=-4.496, -6.685, -4.842, P 0.05)between the uninfected group after craniotomy and the control group. There were no significant differences in the levels of HBP, PCT in CSF and serum PCT (Z=-0.861,-0.514,-0.273, P>0.05)and significant differences in the levels of WBC and neutrophils in CSF(Z=-2.756, -3.060, P<0.05) between the non-bacterial intracranial infection group and the control group. The levels of HBP in CSF in the severe intracranial infection group were significantly higher than those in the mild intracranial infection group(Z=-6.267, P<0.05). The levels of HBP in CSF in the poor prognosis group were significantly higher than those in the good prognosis group(Z=-7.064, P<0.05). The area under the ROC curve for the diagnosis of bacterial intracranial infection by HBP, WBC, neutrophils, TP, PCT in CSF and PCT in serum was 0.986, 0.987, 0.945, 0.945, 0.770 and 0.914, respectively. The area under the ROC curve for differential diagnosis of bacterial intracranial infection and non-bacterial intracranial infection was 0.994, 0.958, 0.961, 0.929, 0.747 and 0.936, respectively. Conclusions HBP in CSF is an ideal indicator for the diagnosis of bacterial intracranial infection. It is important to distinguish between bacterial intracranial infection and non-bacterial intracranial infection. The extent of increase is related to the severity of infection and prognosis of the disease. Key words: Heparin-binding protein; Cerebrospinal fluid; Intracranial infection

Immediate Neutrophil-Variable-T Cell Receptor Host Response in Bacterial Meningitis.

Bacterial meningitis is a life-threatening disease that evokes an intense neutrophil-dominated host response to microbes invading the subarachnoid space. Recent evidence indicates the existence of combinatorial V(D)J immune receptors in neutrophils that are based on the T cell receptor (TCR). Here, we investigated expression of the novel neutrophil TCRαβ-based V(D)J receptors in cerebrospinal fluid (CSF) from human patients with acute-phase bacterial meningitis using immunocytochemical, genetic immunoprofiling, cell biological, and mass spectrometric techniques. We find that the human neutrophil combinatorial V(D)J receptors are rapidly induced in CSF neutrophils during the first hours of bacterial meningitis. Immune receptor repertoire diversity is consistently increased in CSF neutrophils relative to circulating neutrophils and phagocytosis of baits directed to the variable immunoreceptor is enhanced in CSF neutrophils during acute-phase meningitis. Our results reveal that a flexible immune response involving neutrophil V(D)J receptors which enhance phagocytosis is immediately initiated at the site of acute bacterial infection.

Pretreatment Cerebrospinal Fluid Bacterial Load Correlates With Inflammatory Response and Predicts Neurological Events During Tuberculous Meningitis Treatment.

The Mycobacterium tuberculosis load in the brain of individuals with tuberculous meningitis (TBM) may reflect the host's ability to control the pathogen, determine disease severity, and determine treatment outcomes. We used the GeneXpert assay to measure the pretreatment M. tuberculosis load in cerebrospinal fluid (CSF) specimens from 692 adults with TBM. We sought to understand the relationship between CSF bacterial load and inflammation, and their respective impact on disease severity and treatment outcomes. A 10-fold higher M. tuberculosis load was associated with increased disease severity (odds ratio, 1.59; P = .001 for the comparison between grade 1 and grade 3 severity), CSF neutrophil count (r = 0.364 and P < .0001), and cytokine concentrations (r = 0.438 and P < .0001). A high M. tuberculosis load predicted new neurological events after starting treatment (P = .005, by multinomial logistic regression) but not death. Patients who died had an attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations as compared to survivors. In contrast, patients with high pretreatment CSF bacterial loads, cytokine concentrations, and neutrophil counts were more likely to subsequently experience neurological events. The pretreatment GeneXpert-determined M. tuberculosis load may be a useful predictor of neurological complications occurring during TBM treatment. Given the evidence for the divergent pathogenesis of TBM-associated neurological complications and deaths, therapeutic strategies to reduce them may need reassessment.

The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis

BackgroundTick-borne encephalitis (TBE) is a clinically variable but potentially severe Flavivirus infection, with the outcome strongly dependent on secondary immunopathology. Neutrophils are present in cerebrospinal fluid (CSF) of TBE patients, but their pathogenetic role remains unknown. In animal models, neutrophils contributed both to the Flavivirus entry into central nervous system (CNS) and to the control of the encephalitis, which we attempted to evaluate in human TBE.MethodsWe analyzed records of 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114) or meningoencephalomyelitis (n = 16) assessing CSF neutrophil count on admission and at follow-up 2 weeks later, and their associations with other laboratory and clinical parameters. We measured serum and CSF concentrations of Th17-type cytokines (interleukin-17A, IL-17F, IL-22) and chemokines attracting neutrophils (IL-8, CXCL1, CXCL2) in patients with TBE (n = 36 for IL-8, n = 15 for other), with non-TBE aseptic meningitis (n = 6) and in non-meningitis controls (n = 7), using commercial ELISA assays. The results were analyzed with non-parametric tests with p < 0.05 considered as significant.ResultsOn admission, neutrophils were universally present in CSF constituting 25% (median) of total pleocytosis, but on follow-up, they were absent in most of patients (58%) and scarce (< 10%) in 36%. CSF neutrophil count did not correlate with lymphocyte count and blood-brain barrier integrity, did not differ between meningitis and meningoencephalitis, but was higher in meningoencephalomyelitis patients. Prolonged presence of neutrophils in follow-up CSF was associated with encephalitis and neurologic sequelae. All the studied cytokines were expressed intrathecally, with IL-8 having the highest CSF concentration index. Additionally, IL-17A concentration was significantly increased in serum. IL-17F and CXCL1 CSF concentrations correlated with neutrophil count and CXCL1 concentration was higher in patients with encephalitis.ConclusionsThe neutrophil CNS infiltrate does not correlate directly with TBE severity, but is associated with clinical features like myelitis, possibly being involved in its pathogenesis. Th17 cytokine response is present in TBE, especially intrathecally, and contributes to the CNS neutrophilic inflammation. IL-8 and CXCL1 may be chemokines directly responsible for the neutrophil migration.

Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus

BackgroundNeuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF).MethodsLumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined.ResultsTotal protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 levels were significantly elevated compared to controls, while XCL-1 levels remained significantly decreased. Among those with significantly different levels in both absolute and normalized levels, only absolute CCL-19 levels showed a significant correlation with CSF nucleated cells, neutrophils, and lymphocytes. IL-1β and CXCL-10 also were correlated with total cell count, nucleated cells, red blood cells, and neutrophils.ConclusionsNeuroinflammation is likely to be an important process in the pathophysiology of PHH. To our knowledge, this is the first study to investigate CSF levels of chemokines in PHH as well as the only one to show XCL-1 selectively decreased in a diseased state. Additionally, CCL-19 was the only analyte studied that showed significant differences between groups and had significant correlation with cell count analysis. The selectivity of CCL-19 and XCL-1 should be further investigated. Future studies will further delineate the role of these cytokines and chemokines in PHH.

USE OF SCORE AND CEREBROSPINAL FLUID LACTATE DOSAGE IN DIFFERENTIAL DIAGNOSIS OF BACTERIAL AND ASEPTIC MENINGITIS.

ABSTRACTObjective: To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis.Methods: Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis.Results: Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100).Conclusions: 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS.

Clinical Parameters, Routine Inflammatory Markers, and LTA4H Genotype as Predictors of Mortality Among 608 Patients With Tuberculous Meningitis in Indonesia.

Damaging inflammation is thought to contribute to the high morbidity and mortality of tuberculous meningitis (TBM), but the link between inflammation and outcome remains unclear. We performed prospective clinical and routine laboratory analyses of a cohort of adult patients with TBM in Indonesia. We also examined the LTA4H promoter polymorphism, which predicted cerebrospinal fluid (CSF) leukocyte count and survival of Vietnamese patients with TBM. Patients were followed for >1 year. We included 608 patients with TBM, of whom 67.1% had bacteriological confirmation of disease and 88.2% had severe (ie, grade II or III) disease. One-year mortality was 43.7% and strongly associated with decreased consciousness, fever, and focal neurological signs. Human immunodeficiency virus (HIV) infection, present in 15.3% of patients, was associated with higher mortality and different CSF characteristics, compared with absence of HIV infection. Among HIV-uninfected patients, mortality was associated with higher CSF neutrophil counts (hazard ratio [HR], 1.10 per 10% increase; 95% confidence interval [CI], 1.04-1.16), low CSF to blood glucose ratio (HR, 1.16 per 0.10 decrease; 95% CI, 1.04-1.30), CSF culture positivity (HR, 1.37; 95% CI, 1.02-1.84), and blood neutrophilia (HR, 1.06 per 109 neutrophils/L increase; 95% CI, 1.03-1.10). The LTA4H promoter polymorphism correlated with CSF mononuclear cell count but not with mortality (P = .915). A strong neutrophil response and fever may contribute to or be a result of (immuno)pathology in TBM. Aggressive fever control might improve outcome, and more-precise characterization of CSF leukocytes could guide possible host-directed therapeutic strategies in TBM.

Age-specific application of neutrophil-to-lymphocyte ratio in meningitis: a nationwide study.

Cerebrospinal fluid (CSF) neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) are useful in distinguishing bacterial and viral meningitis. Given that meningitis is clinically heterogeneous with regard to age, here we investigated the validity of the CSF NLR and neutrophil assay according to age group. Data from the nationwide referral of >4,000 meningitis cases to the Hellenic Meningitis Reference Laboratory between 2006 and 2013 were examined. CSF NLR and neutrophil counts were stratified according to age, and assay performance was determined using previous cut-off values of 2 and 287 cells/μl for CSF NLR and neutrophils respectively. The distribution of bacterial versus viral meningitis was heterogenous across age groups, with a low proportion of bacterial meningitis in patients aged 5-14. CSF neutrophil count and NLR were significantly more discriminatory for bacterial meningitis in patients aged over 14years than those aged 0-14. The odds ratio (OR), sensitivity, specificity and positive predictive value (PPV) were significantly higher in older patients for both biomarkers. When combined, the false-positive and false-negative detection of bacterial meningitis was 3.9 and 8.5% respectively, and the OR of 262.2 was 2.5-fold greater than expected from a multiplicative effect alone in patients aged >14years. Care is required when applying diagnostic tests for meningitis in different age groups because of patient heterogeneity. This is the first description of the age distribution of meningitis cases in Greece, and knowledge of the age-related distribution of neutrophils and NLR in meningitis cases could help towards developing age-specific meningitis diagnostic assays.

Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.

BackgroundEncephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15–60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.MethodsWe measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.ResultsHeat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001).ConclusionsMediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.

Clinical and Laboratory Findings That Differentiate Herpes Simplex Virus Central Nervous System Disease from Enteroviral Meningitis.

Background. It can be difficult for clinicians to distinguish between the relatively benign enteroviral (EnV) meningitis and potentially lethal herpes simplex virus (HSV) central nervous system (CNS) disease. Very limited evidence currently exists to guide them. Objective. This study sought to identify clinical features and cerebrospinal fluid (CSF) findings associated with HSV CNS disease. Methods. Given that PCR testing often is not immediately available, this chart review study sought to identify clinical and cerebrospinal fluid (CSF) findings associated with HSV meningitis over a 6-year period. In cases where PCR was not performed, HSV and EnV were assigned based on clinical criteria. Results. We enrolled 166 consecutive patients: 40 HSV and 126 EnV patients. HSV patients had a mean 40.4 versus 31.3 years for EnV, p = 0.005, seizures 21.1% versus 1.6% for EnV, p < 0.001, altered mental status 46.2% versus 3.2% for EnV, p < 0.001, or neurological deficits 44.7% versus 3.9% for EnV, p < 0.001. CSF neutrophils were lower in HSV (median 3.0% versus 9.5%, p = 0.0002); median lymphocytes (87.0% versus 67.0%, p = 0.0004) and protein (0.9 g/L versus 0.6 g/L, p = 0.0005) were elevated. Conclusion. Our study found that HSV patients were older and more likely to have seizure, altered mental status, or neurological deficits than patients with benign EnV meningitis. HSV cases had lower CSF neutrophils, higher lymphocytes, and higher protein levels.

Immune cells subpopulations in cerebrospinal fluid and peripheral blood of patients with Aneurysmal Subarachnoid Hemorrhage.

BackgroundThere is growing evidence supporting the role of inflammation in aneurysmal subarachnoid hemorrhage (aSAH) pathophysiology and it is of great interest to elucidate which immune mechanisms are involved.Methods12 aSAH patients and 28 healthy controls were enrolled prospectively. We assessed leukocytes subpopulations and their activation status by flow cytometry in cerebrospinal fluid (CSF) and peripheral blood (PB) of SAH patients at the same time and in PB of controls.ResultsMonocytes and neutrophils were activated in CSF of aSAH patients. The percentage of CD14++CD16+ monocytes were higher in CSF than in PB of aSAH patients, and were also increased in PB of aSAH patients compared with controls. An enhanced expression of CD69 was shown in CSF neutrophils compared with PB in aSAH patients. PB of aSAH patients showed lower percentage of total lymphocytes compared with controls PB. Additionally, lymphocytes were activated in CSF and PB of aSAH patients. CD4+ and CD8+ T cells had a decreased expression on CD3 and higher levels of CD69 in CSF compared with PB in aSAH patients. Moreover, PB CD4+ and CD8+ T cells of aSAH patients were activated compared with controls. Additionally, CD28 expression was decreased on CSF T lymphocytes.ConclusionsOur data suggest an important recruitment of leukocytes to the site of injury in aSAH as well as an increased activation at this level. Overall, these results indicate that aSAH probably stimulates both the innate and adaptive immune responses.

Cerebrospinal fluid lactate in post-neurosurgical bacterial meningitis diagnosis

BackgroundDifferential diagnosis between post-neurosurgical bacterial meningitis (PNBM) and aseptic meningitis is difficult. Inflammatory and biochemical cerebrospinal fluid (CSF) changes mimic those classically observed after CNS surgery. CSF lactate assay has therefore been proposed as a useful PNBM marker. ObjectiveTo evaluate the diagnostic accuracy of CSF lactate as a PNBM marker in patients hospitalized after a neurosurgical procedure. MethodsBetween July 2005 and June 2009, a prospective clinical study, in which all patients with clinical suspicion of PNBM were enrolled, was conducted at our neurosurgical Intensive Care Unit. PNBM diagnosis was categorized as proven, probable or negative before the analysis. ResultsSeventy-nine patients, 51 males with a mean age of 50 years (range 32–68 years) were included. Surgery was elective in 76% patients, mostly for brain tumors (57%); thirty PNBM episodes were identified. CSF parameters were significantly different in glucose concentration (27mg% vs. 73mg%, p<0.001), lactate (8mmol/L vs. 2.8mmol/L, p<0.001), CSF neutrophil pleocytosis (850mm–3 vs. 10mm–3, p<0.001), and protein levels (449mg% vs. 98mg%) between the PNBM and non-PNBM groups. The ROC curve that best fits PNBM diagnosis is lactate. ConclusionIncreased CSF lactate is a useful PNBM marker, with better predictive value than CSF hypoglycorrhachia or pleocytosis. Lactate levels ≥4mmol/L showed 97% sensitivity and 78% specificity, with a 97% negative predictive value.

Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome

Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)-infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART. We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS. Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells ×10(6)/L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4-62.2). The combination of high CSF tumor necrosis factor (TNF)-α and low interferon (IFN)-γ at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53-.99]). TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-γ and TNF-α concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART.

EXTERNAL VALIDATION OF THE BACTERIAL MENINGITIS SCORE IN CHILDREN HOSPITALIZED WITH MENINGITIS

The Bacterial Meningitis Score (BMS) is considered as the rule with the highest sensitivity to safely distinguish between aseptic and bacterial meningitis (BM).Objective: The objective of our study was to evaluate the performance of the score and its usefulness for the clinician.Method: Retrospective analysis of two Belgian academic hospitals-based cohort studies. All consecutive children aged 29 days to 18 years admitted for acute meningitis between January 1996 and December 2008 was eligible. The BMS (risk of bacterial meningitis if seizure, positive cerebrospinal fluid (CSF) Gram staining, CSF protein level 3 80 mg/dl, CSF neutrophil count ≥ 1,000/ mm3 or blood neutrophil count ≥ 10,000/mm3) was applied to all patients with meningitis defined by CSF pleocytosis > 8 WBC/mm3.Results: 174 patients were included in the final analysis of whom 26 (15%) had BM. Of the 93 patients categorized as having with no risk for BM (BMS score = 0), 2 patients had BM, one of which had petechial rash (negative predictive value 97.8%). BMS had a sensitivity of 92.3%. Risk of BM was significantly related to the BMS score: 6/147 (4%) patients with BMS ≤ 1 had BM compared to 20/27 (74%) patients with BMS > 1.Conclusions: Our study reports a lower sensitivity of the BMS than observed in previous validation studies. We suggest to include the BMS in a decision tree aiming to optimize the ordering of laboratory investigations including viral and bacterial PCR testing in any child with CSF pleocytosis.

Evaluation of cerebrospinal fluid parameters in preterm infants with intraventricular reservoirs

Intraventricular reservoirs (IVRs) are used to drain cerebrospinal fluid (CSF) in neonates with post-hemorrhagic ventricular dilatation (PHVD). The objectives of this case-control study were to evaluate changes in CSF parameters in serial IVR taps and to compare CSF parameters in culture-positive and -negative specimens. Clinical and laboratory data from serial (up to 7) reservoir taps at 5- to 8-day intervals were collected on preterm neonates with PHVD and IVR insertion. The median (range) gestational age and birth weight of our cohort (n=52) was 26 (23 to 33) weeks and 796 (450 to 1620) grams. Significant decreases in percentage of CSF neutrophils and protein were noted in later taps, compared with the first tap at insertion of IVR. Five (9.6%) infants had positive CSF cultures on 10 occasions. Compared with negative specimens (n=266), the mean (s.d.) proportion of neutrophils in CSF (55% (33) vs 26% (23)) was significantly higher and ratio of CSF to serum glucose significantly lower (0.19 (0.08) vs 0.29 (0.13)) in culture-positive specimens (n=10). The area under the curve was 0.82 (95% confidence interval (CI) 0.72 to 0.93) for CSF white blood cell (WBC) count, 0.79 (95% CI 0.68 to 0.90) for CSF protein and 0.75 (95% CI 0.56 to 0.95) for percentage of neutrophils. The sensitivities and specificities for diagnosis of infection was 90 and 63% for CSF WBC count > 42 mm(-3), 89 and 58% for CSF protein at > 250 mg dl(-1) and 80 and 67% for CSF neutrophil proportion >31.5%. CSF parameters from IVR taps, specifically proportion of neutrophils and proteins are higher at insertion and progressively normalize over time. Although they vary widely, CSF WBC, protein and neutrophil proportion using higher cut-off values have good sensitivity in the diagnosis of infection.

Clinical Features and Independent Prognostic Factors for Acute Bacterial Meningitis in Adults

Clinical recognition of acute bacterial meningitis (ABM) and its early prognostication would guide the degree of intensive treatment required. We aimed to study the clinical features and factors associated with death in patients with community acquired ABM. Adult patients with clinically suspected community acquired ABM (CAABM) were studied between July 2004 to September 2008 (retrospective and prospective). Detailed history, clinical examination, cerebrospinal fluid (CSF) analysis, and laboratory investigations were performed and noted. The complications with which the patient presented or developed during hospital course were also noted. The outcome noted was at the time of discharge. In multivariate logistic regression, independent factors associated with death were rural area of residence, presentation after >24 h, total leukocyte count (TLC) of <15000, CSF neutrophils <75%, low GCS at the time of admission, and a high creatinine level. In the present study, most of the factors predicting death were identified at the time of admission. Identification of these factors could help prioritizing patients needing intensive care facilities, especially in resource poor setting.