Neutrophils In Cerebrospinal Fluid Research Articles

Predictive performance of cerebrospinal fluid parameters for diagnosis of meningitis in infants: a cohort study

BackgroundThe gold standard for diagnosis of meningitis is the isolation of a pathogen from cerebrospinal fluid (CSF) by culture or PCR. However, treatment is routinely commenced based on CSF findings prior to microbiological results. This study determined the predictive value of CSF parameters for diagnosing bacterial and viral meningitis in young infants.MethodsMulticentre retrospective (2010–2020) cohort study of 1088 CSF results from infants aged 0–90 days. The predictive value of CSF parameters (white blood cell count (WCC), neutrophil, protein, glucose) was evaluated in 538 meningitis cases (39 bacterial, 499 viral) compared with controls with negative CSF microbiological testing and no prior antibiotics.ResultsFor bacterial meningitis, the sensitivity of the commonly used CSF WCC cut-off of 20×106/L for neonates, 15×106/L for infants 1–2 months old and 5×106/L for infants 2–3 months old was 89%, 91% and 86% and the specificity was 78%, 77% and 61%, respectively. CSF protein levels ≥1 g/L in neonates and ≥0.8 g/L in infants aged 1–3 month, or CSF neutrophils ≥2×106/L, independently increased the likelihood of bacterial meningitis (positive likelihood ratios ≥5 and ≥3, respectively). 3 of 39 cases of bacterial meningitis would have been missed using the commonly used WCC cut-offs alone. However, two would have been identified using CSF protein and neutrophil thresholds. All CSF parameters were poor at identifying viral meningitis.ConclusionA single CSF parameter cannot reliably diagnose bacterial meningitis. For identification of bacterial meningitis, elevation of CSF WCC, neutrophil count or protein levels above threshold values improves accuracy of diagnosis.

A comprehensive investigation into the ranges of laboratory tests present in cerebrospinal fluid across various types of meningitis within different age categories

Background. Diagnosing meningitis requires a lumbar puncture to analyze cerebrospinal fluid (CSF) and determine the causative pathogen. Key diagnostic measures include Glucose and Protein concentrations, cell count, differential leukocyte count, Gram stain, culture, and PCR if necessary. Objective. Our analysis assessed patterns in key biomarkers—neutrophils, lymphocytes, cerebrospinal fluid white blood cell count, and CSF/blood Glucose and Protein ratios—across various types of meningitis, including meningococcemia, meningococcal, tuberculous, pneumococcal, aseptic, and other bacterial meningitis. We examined these biomarkers within distinct age categories: children (0-12 years), adults (13-64 years), and the elderly (≥ 65 years). Methods. Descriptive statistics were used to analyze various types of meningitis across different age groups. We assessed the normality of laboratory biomarkers using the Shapiro-Wilk test, and applied Welch ANOVA to explore potential differences in biomarker levels among various types of meningitis. A Games-Howell post hoc test was used to identify specific pairs of meningitis types with statistically significant differences in biomarker levels. Results. The analysis of variance of cerebrospinal fluid biomarkers revealed significant differences in CSF WCC (cells/mm3), Neutrophils (%), Lymphocytes (%), CSF/blood Glucose and Protein ratios in children and adults (p <0.05). However, differences were observed solely in neutrophil levels among elderly subjects. In bacterial meningitis, neutrophil levels increased across all ages, with adults showing higher levels. For meningococcal meningitis, adults had a median neutrophil level of 78.5% [60%, 90%] compared to 57% [24.5%, 85.25%] in children. The CSF white cell count (WCC) median was also higher in adults (339 cells/mm³) compared to children (224 cells/mm³). Viral meningitis cases exhibited higher lymphocyte levels across all age groups, with medians of 69% [34%, 87%] in children, 82% [61%, 93%] in adults, and 77% [55%, 90%] in the elderly. The glucose ratio was lower in bacterial meningitis (<0.3) and higher in viral cases (>0.5). Protein ratios were elevated in bacterial meningitis, indicating increased blood-brain barrier permeability. These results demonstrate a distinct biological profile for different causative agents, modulated by patient age.

Commentary: Cerebrospinal Fluid Neutrophil Gelatinase-Associated Lipocalin as a Novel Biomarker for Post-Neurosurgical Bacterial Meningitis: A Prospective Observational Cohort Study

Commentary: Cerebrospinal Fluid Neutrophil Gelatinase-Associated Lipocalin as a Novel Biomarker for Post-Neurosurgical Bacterial Meningitis: A Prospective Observational Cohort Study

Cerebrospinal Fluid Neutrophil Gelatinase-Associated Lipocalin as a Novel Biomarker for Postneurosurgical Bacterial Meningitis: A Prospective Observational Cohort Study

BACKGROUND AND OBJECTIVES: Postneurosurgical bacterial meningitis (PNBM) was a significant clinical challenge, as early identification remains difficult. This study aimed to explore the potential of neutrophil gelatinase-associated lipocalin (NGAL) as a novel biomarker for the early diagnosis of PNBM in patients who have undergone neurosurgery. METHODS: A total of 436 postneurosurgical adult patients were enrolled in this study. Clinical information, cerebrospinal fluid (CSF), and blood samples were collected. After the screening, the remaining 267 patients were divided into the PNBM and non-PNBM groups, and measured CSF and serum NGAL levels to determine the diagnostic utility of PNBM. Subsequently, patients with PNBM were categorized into gram-positive and gram-negative bacterial infection groups to assess the effectiveness of CSF NGAL in differentiating between these types of infections. We analyzed the changes in CSF NGAL expression before and after anti-infection treatment in PNBM. Finally, an additional 60 patients were included as an independent validation cohort to further validate the diagnostic performance of CSF NGAL. RESULTS: Compared with the non-PNBM group, CSF NGAL was significantly higher in the PNBM group (305.1 [151.6-596.5] vs 58.5 [30.7-105.8] ng/mL; P < .0001). The area under the curve of CSF NGAL for diagnosing PNBM was 0.928 (95% CI: 0.897-0.960), at a threshold of 119.7 ng/mL. However, there was no significant difference in serum NGAL between the 2 groups (142.5 [105.0-248.6] vs 161.9 [126.6-246.6] ng/mL, P = .201). Furthermore, CSF NGAL levels were significantly higher in patients with gram-negative bacterial infections than those with gram-positive bacteria (P = .023). In addition, CSF NGAL levels decrease after treatment compared with the initial stage of infection (P < .0001). Finally, in this validation cohort, the threshold of 119.7 ng/mL CSF NGAL shows good diagnostic performance with a sensitivity and specificity of 90% and 80%, respectively. CONCLUSION: CSF NGAL holds promise as a potential biomarker for the diagnosis, early drug selection, and efficacy monitoring of PNBM.

Neutrophil extracellular trap-associated protein in cerebrospinal fluid for prognosis evaluation of adult bacterial meningitis: a retrospective case-control study.

Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA. We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis. The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition.

Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China.

Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China. A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome-assessed using the modified Barthel disability index-were recorded and compared. A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score ≥ 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (≥15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death. TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

A Specific Pattern of Routine Cerebrospinal Fluid Parameters Might Help to Identify Cases of West Nile Virus Neuroinvasive Disease.

Viral meningitis/encephalitis (ME) is a rare but potentially harmful disease. The prompt identification of the respective virus is important to guide not only treatment but also potential public health countermeasures. However, in about 40% of cases, no virus is identified despite an extensive diagnostic workup. The aim of the present study was to analyze demographic, seasonal, and routine cerebrospinal fluid (CSF) parameters in cases of viral ME and assess their utility for the prediction of the causative virus. Demographic data, season, and routine CSF parameters (total leucocytes, CSF cell differentiation, age-adjusted CSF/serum albumin ratio, and total immunoglobulin ratios) were retrospectively assessed in cases of viral ME. In total, 156 cases of acute viral ME (74 female, median age 40.0 years) were treated at a tertiary-care hospital in Germany. Specific viral infections were detected in 93 (59.6%) cases. Of these, 14 (9.0%) cases were caused by herpes simplex virus (HSV), 36 (23.1%) by varicella-zoster virus (VZV), 27 (17.3%) by enteroviruses, 9 (5.8%) by West Nile virus (WNV), and 7 (4.5%) by other specific viruses. Additionally, 64 (41.0%) cases of ME of unknown viral etiology were diagnosed. Cases of WNV ME were older, predominantly male, showed a severe disruption of the blood-CSF-barrier, a high proportion of neutrophils in CSF, and an intrathecal total immunoglobulin M synthesis in the first CSF sample. In a multinominal logistic regression analysis, the accuracy of these CSF parameters together with age and seasonality was best for the prediction of WNV (87.5%), followed by unknown viral etiology (66.7%), VZV (61.8%), and enteroviruses (51.9%). Cases with WNV ME showed a specific pattern of routine CSF parameters and demographic data that allowed for their identification with good accuracy. These findings might help to guide the diagnostic workup in cases with viral ME, in particular allowing the timely identification of cases with ME due to WNV.

Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection.

Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4weeks estimated gestational age. PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4. Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.

Clinical Characteristics, Treatment, and Outcomes of Veterans with Cerebrospinal Fluid Culture Positive for Gram-Negative Rod Bacteria: A Retrospective Analysis over 18 Years in 125 Veterans Health Administration Hospitals.

Optimal management for patients with bacterial ventriculitis/meningitis due to Gram-negative rods (GNRs) has yet to be well investigated. We assessed the clinical characteristics, treatment, and outcomes of patients with a positive cerebrospinal fluid (CSF) culture for GNRs. We conducted a retrospective cohort study of all patients with a positive CSF culture within the Veterans Health Administration (VHA) system during 2003-2020. Clinical and microbiological characteristics between the true meningitis and contamination groups were compared. Of the 5919 patients with positive CSF cultures among 125 nationwide VHA acute-care hospitals, 297 (5.0%) were positive for GNRs. Among 262 patients analyzed, 156 (59.5%) were assessed as patients with true meningitis, and 106 (40.5%) were assessed as patients with contaminated CSF cultures. Patients with true meningitis had a significantly higher CSF protein (median 168 vs 57mg/dL, p < 0.001), CSF white blood cell count (median 525 vs 3/µL, p = 0.008) and percentage of neutrophils in CSF (median 88 vs 4%, p < 0.001). Enterobacterales were more common in the true meningitis group, while unidentified GNR or polymicrobial CSF cultures were more common in the contamination group. The all-cause 90-day mortality was 25.0% (39/156) in patients with true meningitis and 10.4% (11/106) in those with contaminated CSF cultures. None of the 11 patients with contaminated CSF cultures who died were considered due to missed meningitis. More than 40% of patients with a positive CSF culture with GNR did not receive treatment without negative consequences. Careful clinical judgment is required to decide whether to treat such patients.

Diagnostic Utility of Cerebrospinal Fluid White Blood Cell Components for the Identification of Bacterial Meningitis in Infants.

To evaluate the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU). We identified a cohort of infants discharged from a Pediatrix NICU between 1997 and 2020 who did not have an immunodeficiency, had at least 1 CSF culture collected within the first 120 days of life, and at least 1 CSF laboratory specimen obtained on the day of culture collection. We only included an infant's first CSF culture and excluded cultures from CSF reservoirs and those growing contaminants or nonbacterial organisms. We examined the utility of CSF WBC components to diagnose or predict bacterial meningitis by calculating sensitivity, specificity, positive and negative predictive values, likelihood ratios, and area under the receiver operating curve (AUC) at different cutoff values for each parameter. We performed subgroup analysis excluding infants treated with antibiotics the day before CSF culture collection. Of the 20 756 infants that met the study inclusion criteria, 320 (2%) were diagnosed with bacterial meningitis. We found (AUC [95% CI]) CSF WBC count (0.76 [0.73-0.79]), CSF neutrophil count (0.74 [0.70-0.78]), and CSF neutrophil percent (0.71 [0.67-0.75]) had the highest predictive values for bacterial meningitis, even when excluding infants with early antibiotic administration. No single clinical prediction rule had the optimal discriminatory power for predicting culture-proven bacterial meningitis, and clinicians should be cautious when interpreting CSF WBC parameters in infants with suspected meningitis.

Diagnostic value of cerebrospinal fluid Neutrophil Gelatinase-Associated Lipocalin for differentiation of bacterial meningitis from tuberculous meningitis or cryptococcal meningitis: a prospective cohort study

BackgroundThe early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM) remains a significant clinical challenge. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been reported as a novel inflammatory biomarker in the early stages of infection. This study aimed to investigate whether cerebrospinal fluid (CSF) NGAL can serve as a potential biomarker for distinguishing between BM and TBM or CM.MethodsWe prospectively enrolled the patients with suspected CNS infections at admission and divided them into three case groups: BM (n = 67), TBM (n = 55), CM (n = 51), and an age- and sex-matched hospitalized control (HC, n = 58). Detected the CSF NGAL and assessed its diagnostic accuracy in distinguishing between BM and TBM or CM. Additionally, longitudinally measured the CSF NGAL levels in patients with BM to evaluate its potential as a monitoring tool for antibacterial treatment.ResultsThe concentration of CSF NGAL in BM was significantly higher than in TBM, CM, and HC (all P < 0.05), while the serum NGAL did not show significant differences among the three case groups. The ROC analysis demonstrated that CSF NGAL presented a good diagnostic performance with an AUC of 0.834 (0.770–0.886) and at the optimal cutoff value of 74.27 ng/mL with 70.15% sensitivity and 77.36% specificity for discriminating BM with TBM and CM. Additionally, the CSF NGAL in the convalescent period of BM was significantly lower than in the acute period (P < 0.05).ConclusionsCSF NGAL may serve as a potential biomarker for distinguishing between acute BM and TBM or CM. Additionally, it holds clinical significance in monitoring the effectiveness of antibiotic therapy for BM.

Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis.

Myelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS. This is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (QAlb), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z). MOGAD patients with myelitis were more likely to have a pleocytosis, a QAlb elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, QAlb>10×10-3, as well as higher mean QAlb values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were QAlb>10×10-3 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00). Basic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but QAlb>10×10-3 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria.

A Little Neutrophil Predominance May Not Be a Harbinger of Death: Clinical and Laboratory Characteristics of Meningitis in Jordan.

Background This study aims to evaluate the clinical features, laboratory findings, and outcomes of children and adults diagnosed with meningitis in Jordan. Methodology This is a retrospective chart review study that targeted patients diagnosed with meningitis at King Abdullah University Hospital, a tertiary care center in Northern Jordan, from March 21, 2015, to March 31, 2019. Patients were included in this study if they were older than 28 days and had no risk factors for meningitis. Results A total of 169 patients met the inclusion criteria. Males were overrepresented (67%) and were significantly younger than females (6 vs. 17 years, p = 0.01). Positive meningeal signs were not predictive of greater cerebrospinal fluid leukocytosis (p = 0.348), and they did not provide sufficient sensitivity to be used as screening tools. The most common etiology was aseptic (49%), followed by enterovirus (43%), while bacterial meningitis was an uncommon diagnosis (3.5%). Nearly half of the patients took antibiotics prior to their hospital presentation. During in-hospital admission, six patients died, four of whom had bacterial and two had aseptic meningitis. Enteroviral meningitis showed neutrophil predominance in 44% of cases on lumbar puncture and had a higher neutrophil proportion compared to aseptic meningitis (p = 0.026). Streptococcus pneumoniae was the most common bacterial etiology identified. Conclusions Meningitis in Jordan is most commonly of aseptic and enteroviral origin, and these etiologies carry significantly more favorable outcomes compared to bacterial meningitis. Enteroviral meningitis displays a higher percentage of neutrophils in cerebrospinal fluid compared to aseptic meningitis. S. pneumoniae is the leading cause of bacterial meningitis.Slight neutrophil predominance above halfis a weak predictor of bacterial meningitis due to the small contribution of bacteria asa cause among enteroviruses and aseptic etiologies.

Viral Etiology in Acute Encephalitis Syndrome in North Indian Children

Background and Objective: Acute Encephalitis Syndrome (AES) leads to significant mortality and morbidity in children. This study was undertaken to identify the viral causes of AES and its correlation with clinicodemographic profile. Methods: This cross-sectional study included 100 children aged 1 to 12 years presenting with fever of &lt;14 days duration and a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) and/or new onset of seizures (excluding simple febrile seizures) [1]. Cerebrospinal Fluid (CSF) was collected aseptically by lumbar puncture for biochemical and cytological analysis, and for bacteriological culture. Multiplex PCR for the viruses HSV1, HSV2, Varicella zoster virus, Enterovirus, Mumps and Parecho virus was carried out. Serology for Japanese Encephalitis (JE) was done in blood and CSF by ELISA method. Dengue NS1 antigen and IgM ELISA was carried out in both blood and CSF samples. Serum IgM antibody for scrub typhus was done by ELISA method. Results: Out of 100 children viral cause was detected in 21 patients (Japanese encephalitis -16, Dengue – 4, Varicella zoster virus, Enterovirus and Mumps virus – 1 each). Serum IgM ELISA for scrub typhus was positive in 6 patients. Multiple viral etiology was seen in 2 patients. Mortality was significantly more in females (p=0.021), GCS &lt;8 (p &lt;0.001). Mortality was significantly more with higher CSF neutrophils and higher proteins (p&lt;0.05). Interpretation and Conclusion: This study concludes that viral causes specially JE contributed in AES in North India. Hence viral pathogens including JE needs to be considered as one of major causative agents while treating patients of AES and further emphasis has to be given for JE vaccination in this region.

Neuroinflammatory Biomarkers in Cerebrospinal Fluid From 106 Patients With Recent-Onset Depression Compared With 106 Individually Matched Healthy Control Subjects

BackgroundNeuroinflammation has been linked to depression; however, neuroinflammatory biomarkers in the cerebrospinal fluid (CSF) have not previously been thoroughly investigated in a large group of patients with recent-onset depression compared with healthy control subjects. MethodsWe conducted an individually matched case-control study comparing patients with recent-onset depression (ICD-10: F32) to control subjects. Primary outcomes were CSF white cell count (WCC), CSF-to-serum albumin ratio, CSF total protein, and immunoglobulin G (IgG) index. Secondary outcomes were CSF WCC differential count and CSF neutrophil-to-lymphocyte, CSF-to-serum IgG, and CSF-to-plasma glucose ratios. Linear models adjusting for sex and age were applied. ResultsWe included 106 patients with recent-onset depression (84.0% outpatients) and 106 healthy control subjects. Patients had 18% higher CSF WCC relative to control subjects (relative mean difference [MD]: 1.18; 95% CI: 1.02–1.40; p = .025). CSF WCC differed with depression symptomatology (p = .034), and patients with severe depression (n = 29) had 43% higher CSF WCC relative to control subjects (MD: 1.43; 95% CI: 1.13–1.80, p = .003). Two (1.9%) patients and no controls (0.0%) had CSF WCC above the normal range (>5 × 106/L). No significant differences between groups were observed regarding CSF-to-serum albumin ratio (MD: 1.07; 95% CI: 0.97–1.18; p = .191), CSF total protein (MD: 1.01; 95% CI: 0.94–1.09; p = .775), or IgG index (MD: 1.05; 95% CI: 0.97–1.15; p = .235). Regarding secondary outcomes, the proportion of CSF neutrophils was lower among patients (MD: 0.22; 95% CI: 0.08–0.59; p = .003) relative to control subjects, whereas the remaining outcomes were not significantly different (all p > .06). ConclusionsPatients had higher CSF WCC relative to control subjects, indicating increased neuroimmunologic activation, particularly for severe depression.

The cerebrospinal fluid neutrophil to lymphocyte ratio is a sensitive biomarker for bacterial meningitis in children.

The cerebrospinal fluid neutrophil-to-lymphocyte ratio (CSF NLR) as a diagnostic biomarker of bacterial meningitis has been reported in adult trials. The aim of this study was to evaluate the CSF NLR as a diagnostic biomarker of bacterial meningitis in children and to define an optimal CSF NLR concentration. We performed a retrospective cohort study of children with clinical findings compatible with meningitis. CSF NLR was calculated as the ratio of neutrophil count to lymphocyte count in cerebrospinal fluid (CSF). Initial data included clinical, radiological, and laboratory diagnostics. We determined CSF parameters from children with infectious meningitis (n = 348) and subdivided them into bacterial meningitis (n = 112) and viral meningitis (n = 236). CSF NLR was significantly higher in bacterial meningitis than in viral meningitis (P < 0.001), and its level was higher in Gram-negative bacterial infections than in Gram-positive bacterial infections (P = 0.01). In the receiver operating characteristic curve analysis, CSF NLR was better than CSF protein/sugar/WBC in the ability to distinguish bacterial meningitis from viral meningitis (AUC 0.91 ± 0.02 versus 0.88 ± 0.03/0.87 ± 0.03/0.86 ± 0.03), and using a cutoff point of 0.68, the sensitivity was 0.90, and the specificity was 0.75. Compared with Gram-positive infection, CSF NLR with Gram-negative infection was higher (media, IQR (1.18 (0.19-2.33) versus 3.90 (1.50-8.91), P = 0.01). CSF NLR is a more useful diagnostic tool to distinguish between bacterial meningitis and viral meningitis in children. While at a cutoff value of 0.68, CSF NLR has better sensitivity and specificity for bacterial meningitis, and the higher level of CSF NLR could be related to Gram-negative bacterial infection.

Acute Meningitis in Mansoura Fever Hospital

Background: Meningitis is a serious health problem that results in grave morbidity and mortality. It is caused by several organisms and present with various presenting pictures imparting some challenge. Aim: Highlighting the etiology and prognosis of acute meningitis in Mansoura Fever Hospital. Subjects and Methods: A prospective cross sectional observational study. The study included 350 cases admitted with suspected meningitis. Lumbar puncture: for collection of cerebrospinal fluid (CSF) samples. CSF analysis, microbiological examination of CSF, and blood culture and antibiotic sensitivity test were done. Brain magnetic resonant imaging (MRI) was performed before lumbar puncture in some patients. Detailed analysis of epidemiologic characteristics, clinical data and laboratory findings, the causative organisms, prognosis of all the patients with acute bacterial meningitis (ABM) were studied. Results: Meningitis occurred at all age groups. A significant proportion of meningitis patients (60%) reported a positive history of antibiotic intake in the few days (3-5) before admission to the hospital. 79.1% of ABM patients had a CSF leukocyte count in the range of > 100 up to 1,000 cell/mm3 and 80% had CSF neutrophil percentage > 50%. The pathogens were detected by direct Gram-stained smear in 86.4% of patients. Gram +ve bacteria was detected in 55/110 (50%) of cases. Gram -ve bacteria detected in 40/110 (36.4%) of cases. ABM carried a high mortality rate (22.7%). ABM had 22.7% mortality rate. Conclusions: Meningitis is endemic in Egypt with a significant mortality rate. Strept pneumonia was the most common offending organism.

Diagnostic, predictive and prognostic biomarkers in systemic lupus erythematosus: current insights.

Biomarkers for diagnosis, monitoring and prognosis still constitute an unmet need for systemic lupus erythematosus (SLE). Focusing on recent findings, this review summarises the current landscape of biomarkers in lupus. Urine activated leukocyte cell adhesion molecule (ALCAM) exhibited good diagnostic ability in SLE and lupus nephritis (LN) whereas cerebrospinal fluid neutrophil gelatinase-associated lipocalin (NGAL) showed promise in neuropsychiatric SLE. Urine ALCAM, CD163 and vascular cell adhesion molecule 1 (VCAM-1) may be useful in surveillance of LN. Urine monocyte chemoattractant protein 1 was found to predict treatment response in SLE, and urine CD163 and NGAL treatment response in LN. Serum complement component 3 (C3) and urinary VCAM-1 have been reported to portend long-term renal prognosis in LN. NGAL holds promise as a versatile biomarker in SLE whereas urine ALCAM, CD163 and VCAM-1 displayed good performance as biomarkers in LN. The overall lack of concerted corroboration of leading candidates across multiple cohorts and diverse populations leaves the current biomarker landscape in SLE in an urgent need for further survey and systematic validation.

Incidence and Causative Organisms of Acute Bacterial Meningitis, our Hospital Experience

Aim: To determine the incidence and causative organism of acute bacterial meningitis in patients presented with suspected meningitis Study Design: Cross sectional study Place and duration: This study was conducted in Pakistan Institute of Medical Sciences Islamabad, Pakistan from April 2019 to March 2020. Methodology: A total of 350 patients with suspected meningitis were included in the study. Lumbar puncture is used to obtain samples of the cerebrospinal fluid (CSF). CSF analysis, CSF microbiological inspection, blood culture, and antibiotic sensitivity testing were all performed. In certain individuals, magnetic resonance imaging (MRI) of the brain was conducted prior to lumbar puncture. All patients with acute bacterial meningitis (ABM) had their epidemiologic characteristics, clinical data, and laboratory findings analyzed in detail, as well as the causative organisms and prognosis. Results: Meningitis was found in people of all ages. A considerable number of meningitis patients (60 percent) indicated a positive history of antibiotic use in the days leading up to hospital admission. CSF leukocyte counts in the range of &gt; 100 to 1,000 cell/mm3 were found in 79.1% of ABM patients, while CSF neutrophil percentages were found in 80%. In 86.4 percent of patients, microorganisms were discovered on a direct Gram-stained smear. Gram-positive bacteria were found in 55 of 110 cases (50 percent). Gram-negative bacteria were found in 40 of the 110 cases (36.4 percent). ABM had a high risk of death (22.7 percent). ABM had a mortality rate of 22.7 percent. Conclusions: Meningitis is an endemic disease in our region, with a high fatality rate. Acute bacterial meningitis is very common in patients presenting with suspected meningitis. The most prevalent pathogen was Streptococcus pneumoniae.

Serum and cerebrospinal fluid Neutrophil gelatinase-associated lipocalin (NGAL) levels as biomarkers for the conversion from mild cognitive impairment to Alzheimer's disease dementia

Neutrophil gelatinase-associated lipocalin (NGAL) is an acute phase protein that has been reported as a potential marker for pre-dementia stages of Alzheimer's disease (AD). Longitudinal studies for its association with the conversion of mild cognitive impairment to AD is still lacking. This study included n = 268 study participants with subjective cognitive decline (SCD) (n=82), mild cognitive impairment (MCI) (n=98) and AD dementia (n=88) at baseline and two-year follow-up clinical assessments. Serum and cerebrospinal fluid (CSF)NGAL, CSF amyloid beta1-42, total-Tau, and phospho-Tau levels were measured with ELISA analysis. CSF NGAL levels were significantly lower in MCI participants compared to people with SCD at baseline. Lower baseline CSF NGAL levels predicted MCI converters to AD dementia vs. non-converters after 2-years follow-up. A positive correlation between CSF NGAL and amyloid beta1-42 was found particularly in MCI participants at baseline. NGAL in CSF holds potential to be used as a predictive marker for the conversion of MCI to AD dementia and may reflect pathophysiological processes of prodromal AD neuropathology.