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 Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients with Suspected Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Author(s):  
Rongrong Hua ◽  
Chunyan Liu ◽  
Xing Liu ◽  
Jinwu Zhu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Predictive Value ◽  
Test Group ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Binary Logistic Regression Analysis ◽  
Csf Biomarkers ◽  
Tap Test ◽  
T Tau

Abstract Background: The value of cerebrospinal fluid (CSF) biomarkers for idiopathic normal pressure hydrocephalus (iNPH) needs to be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH, and its predictive value for tap test responsiveness.Methods: Thirty-nine suspected iNPH patients were recruited, contributed qualified CSF, and accepted a tap test and unified pre- and post-test evaluation of neurological function. Results: The analysis of biomarkers from their CSF showed a decrease of tau and its phosphorylated form, especially in the tap test (+) group. In addition, the responsiveness of the tap test was also related to the number of combined symptoms (p<0.01). A correlation was also found between the end pressure or pressure difference of CSF and tap test responsiveness (p<0.05). The results of binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e ^ - (-5.505+55.314 * ratio of p/T-tau - 1.586 * numbers of combined symptoms). The combined indicators (-5.505+0.553* percentage of p/T-tau - 1.586 * numbers of combined symptoms) gave the highest sensitivity and specificity, which were 94.12% and 72.73%, respectively.Conclusions: It may be accessed in judgment of tap test responsiveness, which is beneficial for the feasibility of clinical application.

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 Biomarkers in Idiopathic Normal Pressure Hydrocephalus

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ville Leinonen ◽  
Lata G. Menon ◽  
Rona S. Carroll ◽  
Donna Dello Iacono ◽  
Jeremy Grevet ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Csf Biomarkers ◽  
Cerebrospinal Fluid Biomarkers ◽  
In The Beginning ◽  
Related Proteins ◽  
Selection Of Patients ◽  
Selection Of

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau181, Aβ42, NFL, TNF-α, TGFβ1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result—that is, their gait symptoms improved; 9 patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-αconcentration was low in iNPH patients.

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 Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242321
Author(s):  
Yi Luo ◽  
Nora Möhn ◽  
Amani Al-Mekhlafi ◽  
Sven Schuchardt ◽  
Thomas Skripuletz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Demyelinating Disease ◽  
Statistical Significance ◽  
Virus Detection ◽  
Normal Pressure ◽  
Csf Biomarkers ◽  
Diagnostic Biomarkers ◽  
Metabolomic Profiling ◽  
The Central Nervous System

Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML.

scholarly journals Cerebrospinal fluid amyloid beta and response of cognition to a tap test in idiopathic normal pressure hydrocephalus: a case–control study

2021 ◽  
pp. 1-9
Author(s):  
Hideki Kanemoto ◽  
Etsuro Mori ◽  
Toshihisa Tanaka ◽  
Takashi Suehiro ◽  
Kenji Yoshiyama ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Beta ◽  
Normal Pressure Hydrocephalus ◽  
Case Control Study ◽  
Normal Pressure ◽  
Case Control ◽  
Csf Biomarkers ◽  
Tap Test ◽  
Total Tau ◽  
Control Study

ABSTRACT Objectives: To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH). Design: Case–control study. Setting: Osaka University Hospital. Participants: Patients with possible iNPH underwent a CSF tap test. Measurements: Concentrations of amyloid beta (Aβ) 1–40, 1–42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aβ1–42 to Aβ1–40 (Aβ42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients. Results: We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aβ42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aβ42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aβ42/40 ratio. The association between Aβ42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline. Conclusions: A low CSF Aβ42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.

scholarly journals Cerebrospinal fluid analysis in 108 patients with progressive multifocal leukoencephalopathy

2020 ◽  
Author(s):  
Nora Möhn ◽  
Luo Yi ◽  
Thomas Skripuletz ◽  
Philipp Schwenkenbecher ◽  
Anne Ladwig ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cell Count ◽  
Normal Pressure ◽  
Control Group ◽  
Fluid Analysis ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
Insight Into

Abstract Background: Progressive multifocal leukoencephalopathy (PML) is caused by an opportunistic infection with JC polyoma virus (JCPyV) and mainly affects immunocompromised patients. It leads to pronounced demyelination of the central nervous system (CNS) resulting in severe disability or even death. Detection of JCPyV DNA in the cerebrospinal fluid (CSF) is usually accepted as proof for the diagnosis of PML. Routine CSF parameters, like CSF cell count, protein concentration, Qalbumin, or intrathecal immunoglobulin synthesis are mostly considered normal. However, this has not been investigated systematically. Methods: We analyzed routine CSF parameters in a cohort of 108 PML patients that were treated at four different neurological centers in Germany. The patients exhibited different underlying conditions with natalizumab-treated multiple sclerosis (n=54) and human immunodeficiency virus (HIV)-infection (n=25) being the most frequent. The data were collected at the respective centers in accordance with local requirements and then jointly analyzed. The total PML cohort was compared with a control group of patients with normal pressure hydrocephalus (NPH) and idiopathic intracranial hypertension (IIH). Multiple sclerosis and HIV patients were additionally compared with their own non-PML control groups. Results: The PML group showed an elevated cell count (p<0.001) compared to the control group, however, this effect was mainly driven by HIV-PML patients. This subgroup also demonstrated a significantly higher proportion of patients with a disturbed blood-CSF-barrier function. Conclusions: This comprehensive, retrospective study on CSF diagnostic analysis in PML patients provides insight into the CSF of those patients. It demonstrates that CSF composition in PML patients may be specific for the underlying condition that predisposes for the development of PML and thus data have to be interpreted in this context.

scholarly journals Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Vol 13 ◽  
Author(s):  
Rongrong Hua ◽  
Chunyan Liu ◽  
Xing Liu ◽  
Jinwu Zhu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Predictive Value ◽  
Clinical Symptoms ◽  
Test Group ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Binary Logistic Regression Analysis ◽  
Csf Biomarkers ◽  
Tap Test

Background: The value of cerebrospinal fluid (CSF) biomarkers for assessing idiopathic normal pressure hydrocephalus (iNPH) must be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH and the predictive value of these biomarkers for tap test responsiveness.Methods: Thirty-nine patients with suspected iNPH were recruited, contributed qualified CSF, and underwent a tap test and unified pre- and post-test evaluations of the neurological function.Results: The analysis of biomarkers from the patients’ CSF showed decreased levels of tau and its phosphorylated form, especially in the tap test (+) group. The responsiveness of the tap test was also related to the number of combined symptoms (p &lt; 0.01), and a correlation was found between the end pressure or pressure difference in CSF and tap test responsiveness (p &lt; 0.05). The results of the binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e∧ − (−5.505 + 55.314 * ratio of p/T-tau − 1.586 * numbers of combined symptoms). The combined indicators (−5.505 + 0.553 * percentage of p/T-tau − 1.586 * numbers of combined symptoms) resulted in the highest sensitivity and specificity of 94.12% and 72.73%, respectively.Conclusions: CSF biomarkers may be assessed to judge tap test responsiveness, which is beneficial for the feasibility of a clinical application.

scholarly journals Cerebrospinal Fluid Biomarkers as Predictors of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review

2017 ◽  
Vol 45 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Tyler Pfanner ◽  
Alexandre Henri-Bhargava ◽  
Stephanie Borchert
Keyword(s):  
Systematic Review ◽  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Future Research ◽  
Csf Biomarkers ◽  
Level Of Evidence ◽  
Shunt Procedure ◽  
Shunt Response

ABSTRACTBackground: The widely accepted treatment for idiopathic normal-pressure hydrocephalus (iNPH) is a cerebrospinal fluid (CSF) diversion shunt procedure, to which approximately 80% of patients will respond. The purpose of this systematic review was to identify which CSF biomarkers have been investigated in predicting shunt responsiveness in iNPH patients, and to analyze the level of evidence for each. Methods: To find all relevant articles, a comprehensive search of Medline, Embase, and PsycINFO was conducted. Results: The literature search identified 344 unique citations, of which 13 studies satisfied the inclusion criteria and were analyzed in our review. These 13 studies reported on 37 unique biomarkers. Conclusions: The available studies suggest that there is evidence for the utility of CSF biomarkers in predicting shunt responsiveness in iNPH patients, though none have been shown to predict shunt response with both high sensitivity and specificity. We found that there is no available evidence for the use of Aβ38, Aβ40, Aβ43, APL1β25, APL1β27, APL1β28, sAPP, aAPPα, sAPPβ, TNF-α, MCP-1, sCD40L, sulfatide, MBP, L-PGDS, cystatin C, transthyretin, TGF-β2, or YKL-40 in predicting shunt response. There is minimal evidence for the use of TGF-β1, TBR-II, homocysteine, and interleukins (particularly IL-1β, IL-6, and IL-10). However, the available evidence suggests that these biomarkers warrant further investigation. Aβ42, tau, p-tau, NFL, and LRG have the greatest amount of evidence for their predictive value in determining shunt responsiveness in iNPH patients. Future research should be guided by, but not limited to, these biomarkers.

Cerebrospinal fluid white cell count: discriminatory or otherwise for enteroviral meningitis in infants and young children?

2015 ◽  
Vol 22 (2) ◽  
pp. 213-217 ◽  
Author(s):  
Natalie Woon Hui Tan ◽  
Elis Yuexian Lee ◽  
Gloria Mei Chin Khoo ◽  
Nancy Wen Sim Tee ◽  
Subramania Krishnamoorthy ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Young Children ◽  
Cell Count ◽  
White Cell Count ◽  
White Cell ◽  
Enteroviral Meningitis ◽  
Infants And Young Children
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