scholarly journals Phosphatidylcholine PC ae C44:6 in cerebrospinal fluid is a sensitive biomarker for bacterial meningitis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Leonardo Silva de Araujo ◽  
Kevin Pessler ◽  
Kurt-Wolfram Sühs ◽  
Natalia Novoselova ◽  
Frank Klawonn ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Cell Count ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Characteristic Curve ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Membrane Phospholipids ◽  
Cns Disorders

Abstract Background The timely diagnosis of bacterial meningitis is of utmost importance due to the need to institute antibiotic treatment as early as possible. Moreover, the differentiation from other causes of meningitis/encephalitis is critical because of differences in management such as the need for antiviral or immunosuppressive treatments. Considering our previously reported association between free membrane phospholipids in cerebrospinal fluid (CSF) and CNS involvement in neuroinfections we evaluated phosphatidylcholine PC ae C44:6, an integral constituent of cell membranes, as diagnostic biomarker for bacterial meningitis. Methods We used tandem mass spectrometry to measure concentrations of PC ae C44:6 in cell-free CSF samples (n = 221) from patients with acute bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis (herpes simplex virus, varicella zoster virus, enteroviruses), autoimmune neuroinflammation (anti-NMDA-receptor autoimmune encephalitis, multiple sclerosis), facial nerve and segmental herpes zoster (shingles), and noninflammatory CNS disorders (Bell’s palsy, Tourette syndrome, normal pressure hydrocephalus). Results PC ae C44:6 concentrations were significantly higher in bacterial meningitis than in all other diagnostic groups, and were higher in patients with a classic bacterial meningitis pathogen (e.g. Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus) than in those with less virulent or opportunistic pathogens as causative agents (P = 0.026). PC ae C44:6 concentrations were only moderately associated with CSF cell count (Spearman’s ρ = 0.45; P = 0.009), indicating that they do not merely reflect neuroinflammation. In receiver operating characteristic curve analysis, PC ae C44:6 equaled CSF cell count in the ability to distinguish bacterial meningitis from viral meningitis/encephalitis and autoimmune CNS disorders (AUC 0.93 both), but had higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%). A diagnostic algorithm comprising cell count, lactate and PC ae C44:6 had a sensitivity of 97% (specificity 87%) and negative predictive value of 99% (positive predictive value 61%) and correctly diagnosed three of four bacterial meningitis samples that were misclassified by cell count and lactate due to low values not suggestive of bacterial meningitis. Conclusions Increased CSF PC ae C44:6 concentrations in bacterial meningitis likely reflect ongoing CNS cell membrane stress or damage and have potential as additional, sensitive biomarker to diagnose bacterial meningitis in patients with less pronounced neuroinflammation.

scholarly journals Diagnostic accuracy of cerebrospinal fluid lactate in confirmed cases of acute bacterial meningitis in children

2020 ◽  
Vol 36 (7) ◽  
Author(s):  
Hina Nasir ◽  
Muhammad Faheem Afzal ◽  
Muhammad Haroon Hamid ◽  
Akmal Laeeq
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Diagnostic Accuracy ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Lactate Level ◽  
Acute Bacterial Meningitis ◽  
Csf Lactate ◽  
Meningitis In Children ◽  
Sensitivity Specificity

Objective: To determine the diagnostic accuracy of cerebrospinal fluid lactate level in confirmed cases of acute bacterial meningitis in children Methods: This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/ Mayo Hospital, Lahore from January to December 2018. A total of 250 children, between two months - 12 years of age, of both the genders, with suspected acute bacterial meningitis were included by non-probability consecutive sampling. Each child was subjected to lumbar puncture for biochemistry, cytology, culture, and lactate level. CSF lactate level of 1.1-2.4 mmol/L was taken as normal, and >2.4 mmol/L was taken as cut off for acute bacterial meningitis. All collected data was entered and analyzed in SPSS version 22. A 2 x 2 table was made to calculate diagnostic accuracy, sensitivity, specificity, positive and negative predictive value for CSF Lactate. Results: The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of CSF lactate taking CSF culture as gold standard was 100%, 60.61%, 17.27%, 100% and 63.6% respectively, with kappa of 0.19 and p value of 0.000. Conclusion: At a cut off value of 2.4 mmol/L, cerebrospinal fluid lactate level has a high diagnostic accuracy for acute bacterial meningitis. doi: https://doi.org/10.12669/pjms.36.7.1682 How to cite this:Nasir H Afzal MF, Hamid MH, Laeeq A. Diagnostic accuracy of cerebrospinal fluid lactate in confirmed cases of acute bacterial meningitis in children. Pak J Med Sci. 2020;36(7):---------. doi: https://doi.org/10.12669/pjms.36.7.1682 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anahita Bakochi ◽  
Tirthankar Mohanty ◽  
Paul Theodor Pyl ◽  
Carlos Alberto Gueto-Tettay ◽  
Lars Malmström ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Host Response ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Tissue Cell ◽  
Response Patterns ◽  
Lasso Regression ◽  
Specific Host

Meningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.

scholarly journals A Diagnostic Scoring System for Distinguishing between Tuberculous and Bacterial Meningitis Based on Clinical and Laboratory Findings

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yongyan He ◽  
Yueli Zou ◽  
Junying He ◽  
Hui Bu ◽  
Yaling Liu
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Cell Count ◽  
Tuberculous Meningitis ◽  
Scoring System ◽  
White Cell Count ◽  
Characteristic Curve ◽  
Chinese Patients ◽  
Laboratory Findings ◽  
Microbial Resources

It is very difficult to diagnose and distinguish tuberculous meningitis, and the current laboratory methods are unsubstantial in developing countries. The study is aimed at creating a scoring system on the basis of basic laboratory and clinical achievements that could be used as diagnostic aid for tuberculous meningitis for Chinese patients. A retrospective study of cases was conducted for comparison between clinical characteristics and laboratory features of 241 patients on admission who conformed to inclusion criteria of tuberculous meningitis ( n = 141 ) or bacterial meningitis ( n = 100 ). Logistic regression was employed to establish a diagnostic formula to distinguish between tuberculous meningitis and bacterial meningitis. The receiver operating characteristic curve analysis was applied to determine the best diagnostic critical point of the diagnostic formula. It was found that five variables (disease course, white blood cell count, serum sodium, total white cell count of cerebrospinal fluid, and neutrophil proportion in cerebrospinal fluid) were independently associated with tuberculous meningitis. The 87% sensitivity and 94% specificity were included in the diagnostic scoring system derived from these variables. Especially in the case of limited microbial resources, doctors can use this diagnostic scoring system to distinguish tuberculous meningitis from bacterial meningitis.

scholarly journals Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis

2020 ◽  
Author(s):  
Anahita Bakochi ◽  
Tirthankar Mohanty ◽  
Paul Theodor Pyl ◽  
Lars Malmström ◽  
Adam Linder ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Host Response ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Tissue Cell ◽  
Response Patterns ◽  
Lasso Regression ◽  
Specific Host

AbstractMeningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.

The Use of Cytokine and C-Reactive Protein Measurements in Cerebrospinal Fluid during Acute Infective Meningitis

1994 ◽  
Vol 31 (3) ◽  
pp. 255-261 ◽  
Author(s):  
M Stearman ◽  
H J Southgate
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
White Cell Count ◽  
Correct Diagnosis ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Control Group ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Factor Α

Cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP), tumour necrosis factor α (TNF), interleukin-6 (IL-6), total protein (TP) and white cell count with differential (WCC) have been measured in 24 patients presenting with acute bacterial or viral meningitis and also in a non-infected, non-inflammed control group ( n = 24). In acute viral meningitis, CRP levels were not raised when compared to controls and there was a discordance between high levels of the primary inflammatory mediators (IL-6 and TNF) and the low measured CRP levels. CRP levels were raised in cases of bacterial meningitis. A concentration of 100 ng/mL CRP had a sensitivity of 87% for bacterial meningitis. TNF concentrations in the CSF were significantly raised in cases of acute bacterial meningitis ( P < 0·001). Smaller but variable elevations were seen in the patients with acute viral meningitis. One patient, who succumbed to bacterial infection, showed low CSF levels of CRP, TNF and WCC but an elevated IL-6 concentration. Another, presenting with low CSF WCC, had raised concentrations of CRP, TNF and IL-6 which pointed to the correct diagnosis of acute bacterial meningitis. The development of methods yielding rapid analysis for these cytokines together with a sensitive assay for CRP in CSF would be a useful adjunct to conventional investigation.

Neurotrophin-3 Levels in Cerebrospinal Fluid From Children With Bacterial Meningitis, Viral Meningitis, or Encephalitis

2000 ◽  
Vol 15 (1) ◽  
pp. 19-21 ◽  
Author(s):  
Yumi Mizuno ◽  
Hidetoshi Takada ◽  
Kyoko Urakami ◽  
Kenji Ihara ◽  
Ryutaro Kira ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Viral Meningitis ◽  
Neurotrophin 3

Abstract 150: Multicenter Validation of SPOT, an Artificial Intelligence Based Tool, to Optimize Selection of Elderly Stroke Patients for Mechanical Thrombectomy - Insights From the STAR Collaboration

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ali M Alawieh ◽  
Mohamed Baker Alawieh ◽  
Fadi Zaraket ◽  
Reda M Chalhoub ◽  
Mohammad Anadani ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Mechanical Thrombectomy ◽  
Characteristic Curve ◽  
Linear Regression Models ◽  
Good Outcome ◽  
Poor Outcome ◽  
Multicenter Validation ◽  
Selection Of

Introduction: Mechanical thrombectomy for acute ischemic stroke (AIS) is the current standard of care based on level 1 evidence from multiple randomized controlled trials. Recently, real-world indications for mechanical thrombectomy (MT) has extended beyond the inclusion criteria used in the majority of trials including elderly patients. We have recently developed a machine-learning based tool, SPOT, to optimize selection of elderly patients for MT based on single-center data. Here, we use a large cohort of international multicenter patients who underwent MT for AIS to externally validate SPOT. Methods: Patients who underwent MT for AIS at 12 comprehensive stroke centers in the US and Europe between 01/2013 and 12/2018 were reviewed. Patients age 80 years or older were included for validation of SPOT. SPOT is designed based on a combination of decision trees and linear regression models to provide binary output of predicted good (mRS 0-2) or poor outcome (mRS 3-6) after MT. SPOT uses admission variables: age, gender, comorbidities, admission NIHSS, baseline mRS score, ASPECT score and whether IV-tPA was administered. Predicted outcome was compared to actual outcome recorded at 90-days after treatment. A receiver operating characteristic curve was used to evaluate the accuracy of SPOT, and the negative predictive value was computed. The rate of post-procedural hemorrhage and mortality were compared between patients predicted by SPOT to have good versus poor outcome. Results: A total of 3,228 patients underwent MT for AIS during the study duration, of which 647 patients were at least 80 years of age or older and were included in the study. The average age was 85±5 years, and 65% were females. The median mRS score at 90 days was 4, and 21.3% had a good outcome (mRS 0-2). Of patients predicted by SPOT to have a poor outcome, 90% had a poor outcome. The area under the ROC curve was 0.7. The mortality rate in patients predicted by SPOT to have poor outcome had twice higher mortality than those predicted to have good outcome (55% vs 27%, p<0.001). Conclusions: Based on multicenter validation, SPOT presents a clinical decision in aid in assisting for exclusion of elderly patients unlikely to benefit from MT for AIS with a 90% negative predictive value.

scholarly journals Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy

2003 ◽  
Vol 47 (10) ◽  
pp. 3104-3108 ◽  
Author(s):  
Federico Pea ◽  
Federica Pavan ◽  
Ennio Nascimben ◽  
Claudio Benetton ◽  
Pier Giorgio Scotton ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Steady State ◽  
Bacterial Meningitis ◽  
Acute Bacterial Meningitis ◽  
Terminal Phase ◽  
Communicating Hydrocephalus ◽  
Synergistic Activity ◽  
Dosing Interval ◽  
Concentration Time ◽  
Meningeal Inflammation

ABSTRACT In vitro levofloxacin exhibits both potent or intermediate activity against most of the pathogens frequently responsible for acute bacterial meningitis and synergistic activity with some beta-lactams. Since levofloxacin was shown to penetrate the cerebrospinal fluid (CSF) during meningeal inflammation both in animals and in humans, the disposition of levofloxacin in CSF was studied in 10 inpatients with external ventriculostomy because of communicating hydrocephalus related to subarachnoid occlusion due to cerebral accidents who were treated with 500 mg of levofloxacin intravenously twice a day because of extracerebral infections. Plasma and CSF concentration-time profiles and pharmacokinetics were assessed at steady state. Plasma and CSF levofloxacin concentrations were analyzed by high-pressure liquid chromatography. The peak concentration of levofloxacin at steady state (C max ss)was 10.45 mg/liter in plasma and 4.06 mg/liter in CSF, respectively, with the ratio of the C max ss in CSF to the C max ss in plasma being 0.47. The areas under the concentration-time curves during the 12-h dosing interval (AUC0-τs) were 47.69 mg · h/liter for plasma and 33.42 mg · h/liter for CSF, with the ratio of the AUC0-τ for CSF to the AUC0-τ for plasma being 0.71. The terminal-phase half-life of levofloxacin in CSF was longer than that in plasma (7.02 ± 1.57 and 5.51 ± 1.36 h, respectively; P = 0.034). The ratio of the levofloxacin concentration in CSF to the concentration in plasma progressively increased with time, from 0.30 immediately after dosing to 0.99 at the end of the dosing interval. In the ventricular CSF of patients with uninflamed meninges, levofloxacin was shown to provide optimal exposure, which approximately corresponded to the level of exposure of the unbound drug in plasma. The findings provide support for trials of levofloxacin with twice-daily dosing in combination with a reference beta-lactam for the treatment of bacterial meningitis in adults. This cotreatment could be useful both for overcoming Streptococcus pneumoniae resistance and for enabling optimal exposure of the CSF to at least one antibacterial agent for the overall treatment period.

Cerebrospinal Fluid Leucine-Rich Alpha-2 Glycoprotein (LRG) Levels in Children with Acute Bacterial Meningitis

2021 ◽  
Author(s):  
Kushal Talukder ◽  
Rajniti Prasad ◽  
Abhisek Abhinay ◽  
Ankur Singh ◽  
Ragini Srivastava ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Acute Bacterial Meningitis
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