scholarly journals Comparison of Cerebrospinal Fluid Biomarkers for Differential Diagnosis of Acute Bacterial and Viral Meningitis with Atypical Cerebrospinal Fluid Characteristics

2019 ◽  
Vol 29 (3) ◽  
pp. 244-254 ◽  
Author(s):  
Sérgio Monteiro de Almeida ◽  
Suélen Maria Parizotto Furlan ◽  
Arianne Maris Munhoz Cretella ◽  
Bruna Lapinski ◽  
Keite Nogueira ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Positive Likelihood Ratio ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Blood Levels ◽  
Csf Biomarkers ◽  
Control Groups ◽  
Easy Method ◽  
Csf Lactate

Objective: Several cerebrospinal fluid (CSF) biomarkers are used to distinguish between acute bacterial meningitis (BM) and viral meningitis (VM). We compared the ability of lactate and glucose (GL) in CSF and the CSF/blood GL ratio to distinguish between acute BM and VM with typical and atypical CSF characteristics. Methods: Three hundred and twenty-four CSF reports were included, which were distributed as the acute BM, VM, and normal control groups (n = 63, 139, and 122, respectively). Results: Lactate level in the CSF of acute BM group was 4-fold higher than that in the acute VM and control groups (p < 0.0001). CSF lactate presented higher specificity (92%) and negative predictive value (94%) compared to CSF GL and CSF/blood GL ratio in distinguishing acute BM and VM. Definitive acute BM or VM with atypical CSF cell characteristics was observed in 23.2 and 21.6% of samples, respectively, and these groups showed reduced performance of characteristics of all CSF biomarkers. CSF lactate showed better operational characteristics than those of CSF GL and CSF/blood GL ratio, presenting the highest positive likelihood ratio, and thus aided in the differential diagnosis of VM with atypical CSF. Conclusion: The CSF lactate assay can be routinely used in laboratories as a rapid, automated, and easy method that is independent of lactate blood levels.

scholarly journals Comparison of cerebrospinal fluid lactate with physical, cytological, and other biochemical characteristics as prognostic factors in acute bacterial meningitis

2019 ◽  
Vol 77 (12) ◽  
pp. 871-880
Author(s):  
Sérgio Monteiro De Almeida ◽  
Nagyla C. Barros ◽  
Ricardo Petterle ◽  
Keite Nogueira
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Lactate Concentration ◽  
Good Prognosis ◽  
Acute Bacterial Meningitis ◽  
Csf Biomarkers ◽  
High Morbidity ◽  
Initial Hypothesis ◽  
Csf Lactate ◽  
Lactate Levels

ABSTRACT Bacterial meningitis (BM) is associated with a high morbidity and mortality. Cerebrospinal fluid (CSF) lactate may be used as a prognostic marker of this condition. We hypothesized that CSF lactate levels would remain elevated in participants who died of acute BM compared with those who recovered from this disease. Objective: To evaluate the potential use of lactate and other CSF biomarkers as prognostic markers of acute BM outcome. Methods: This retrospective, longitudinal study evaluated dynamic CSF biomarkers in 223 CSF samples from 49 patients who fulfilled the inclusion criteria of acute BM, with bacteria identified by CSF culturing. The participants were grouped according to outcome: death (n = 9; 18.37%) and survival (n = 40; 81.63%). All participants received appropriate antibiotic treatment. Results: In the logistic regression model, lactate concentration in the final CSF sample, xanthochromia, and CSF glucose variation between the first and last CSF samples were predictors of a poor outcome (death). In contrast, decrease in CSF white blood cell count and CSF percentage of neutrophils, increase in the percentage of lymphocytes, and normalization of the CSF lactate concentration in the last CSF sample were predictors of a good prognosis. Conclusion: The study confirmed the initial hypothesis. The longitudinal analysis of CSF lactate is an important predictor of prognosis in acute BM.

Clinical performance of amperometry compared with enzymatic ultra violet method for lactate quantification in cerebrospinal fluid

Diagnosis ◽  
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sérgio Monteiro de Almeida ◽  
Nagyla Barros ◽  
Alisson Fernandes dos Santos ◽  
Gislaine Custodio ◽  
Ricardo Rasmussen Petterle ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Performance ◽  
Ultra Violet ◽  
Viral Meningitis ◽  
Limited Resources ◽  
Acute Bacterial Meningitis ◽  
Amperometric Method ◽  
Wide Range ◽  
Csf Lactate ◽  
Range Of Values

AbstractObjectivesThe differential diagnosis between acute bacterial meningitis (BM) and viral meningitis (VM) is crucial for treatment and prognosis. Cerebrospinal fluid (CSF) lactate (LA) is considered a good biomarker for differentiating BM from VM. The objective of this study was to compare the clinical performance of amperometry, which is not validated for measurement of LA in CSF samples, with a validated method (enzymatic ultra violet), for their ability to discriminate between acute BM and VM.MethodsIt was a retrospective, descriptive comparative study, 320 CSF reports were included; LA was quantified in CSF using either Dimension AR machine (Dade Behring) or amperometry (RAPID Point 500, Siemens). All samples with bacteria (n=54) or virus (n=139) identified, compared with a control with normal CSF (n=127).ResultsCSF LA levels were comparable for amperometry or enzymatic methods on each group studied, in a wide range of LA levels; it was capable to distinguish BM from VM independent of the method used to quantify.ConclusionsThe findings support the use of the amperometric method in measuring LA concentrations in CSF in a wide range of values. Amperometry is a less expensive method, validated for blood, easily available in small laboratories including in limited resources countries.

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 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 Identification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis

2019 ◽  
Vol 20 (2) ◽  
pp. 337 ◽  
Author(s):  
Dominica Ratuszny ◽  
Kurt-Wolfram Sühs ◽  
Natalia Novoselova ◽  
Maike Kuhn ◽  
Volkhard Kaever ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cell Count ◽  
Normal Pressure ◽  
Viral Meningitis ◽  
Metabolic Reprogramming ◽  
Diagnostic Tools ◽  
Csf Biomarkers ◽  
Metabolite Profiles ◽  
Enteroviral Meningitis ◽  
Combined Classifier

Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis (n = 10), and subdivided them into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell’s palsy and normal pressure hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other Central nervous system (CNS) infections.

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.

Meningitis Due to Mumps Virus in a Child with Acute Leukemia

PEDIATRICS ◽  
1970 ◽  
Vol 46 (6) ◽  
pp. 942-945
Author(s):  
Lothar M.T. Rupprecht ◽  
J. Lawrence Naiman
Keyword(s):  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Virus Infection ◽  
Acute Leukemia ◽  
Cell Count ◽  
Mononuclear Cell ◽  
Viral Meningitis ◽  
Mumps Virus ◽  
Leukemic Infiltration ◽  
Cerebrospinal Fluid Examination

An 8½-year-old boy with leukemia in remission developed a meningitis-like syndrome associated with increased mononuclear cell count in the cerebrospinal fluid. Examination of the stained CSF sediment showed these to be small lymphocytes rather than lymphoblasts, suggesting a diagnosis of viral meningitis rather than leukemic infiltration of the meninges. Serologic studies gave evidence of a recent mumps virus infection. Viral meningitis should not be overlooked in the differential diagnosis of meningeal reactions in children with leukemia.

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