Special Issue "Novel Insights on Cerebrospinal Fluid Research"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (1 October 2021).

Special Issue Editors

Prof. Dr. Thomas Skripuletz
E-Mail Website
Guest Editor
Department of Neurology,Hannover Medical School, Hannover, Germany
Interests: immune mediated neuropathies; Neuro-Sjögren; multiple sclerosis; neuroimmuno-oncology; neuroinfectious diseases; neuroimmunology
Dr. Alexandra Neyazi
E-Mail Website
Guest Editor
Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
Interests: psychoneuroimmunology; multiple sclerosis; affective disorders; cerebrospinal fluid research; epigenetics; psychiatric biomarkers

Special Issue Information

Dear Colleagues,

Cerebrospinal fluid (CSF) analysis is an essential diagnostic tool in a high number of neurological and psychiatric diseases. This includes predominantly autoimmune, infectious, and neurodegenerative diseases of the central and peripheral nervous system. However, psychiatrists increasingly are involved in this relevant research topic. 

Since 2017, CSF oligoclonal bands have been used as a part of the McDonald criteria to diagnose multiple sclerosis. This new diagnostic approach has led to a relevant change in the sensitivity of the criteria to diagnose multiple sclerosis. In the last two years, several groups have shown that multiple sclerosis can be now diagnosed more frequently at the time of first clinical relapse, underlining the importance of incorporating CSF analysis.

The important role of CSF examination and disease monitoring has arisen in further diseases, including autoimmune encephalitis driven by autoantibodies directed against neuronal structures such as the N-methyl-D-aspartate (NMDA) receptor. Patients with such diseases are treated in both neurology and psychiatry. Still, further experimental research is needed to obtain a better understanding of this severe disease entity.

This Special Issue of Cells is dedicated to the complete experimental research on CSF in neurologic and psychiatric diseases. There is a need to identify new biomarkers, including cellular research for most neurological and psychiatric diseases. We look forward for your contribution to this intensely developing area of research.

Prof. Dr. Thomas Skripuletz
Dr. Alexandra Neyazi
Guest Editors

Manuscript Submission Information

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Keywords

  • CSF biomarker
  • kappa free light chains (KFLC)
  • cellular research
  • biomarker
  • neuroimmunology
  • psychoneuroimmunology
  • infection
  • multiple sclerosis
  • psychiatry
  • autoimmune disease

Published Papers (5 papers)

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Research

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Article
Profiling Complement System Components in Primary CNS Vasculitis
Cells 2021, 10(5), 1139; https://doi.org/10.3390/cells10051139 - 08 May 2021
Cited by 1 | Viewed by 739
Abstract
Complement activation has been implicated in the pathogenesis of many vasculitic syndromes such as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Using an array-based multiplex system, we simultaneously quantified serum and CSF levels of activated and regulatory complement system proteins in patients with primary CNS [...] Read more.
Complement activation has been implicated in the pathogenesis of many vasculitic syndromes such as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Using an array-based multiplex system, we simultaneously quantified serum and CSF levels of activated and regulatory complement system proteins in patients with primary CNS vasculitis (PACNS; n = 20) compared to patients with non-inflammatory conditions (n = 16). Compared to non-inflammatory controls, levels of C3a, C5a, and SC5b-9, indicative for general activation of the complement system, of C4a, specific for the activation of the classical pathway, Ba and Bb, reflective for alternative complement activation as well as concentrations of complement-inhibitory proteins factor H and factor I were unchanged in patients with PACNS. Our study does not support the hypothesis that complement activation is systemically increased in patients with PACNS. Full article
(This article belongs to the Special Issue Novel Insights on Cerebrospinal Fluid Research)
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Article
Kappa Free Light Chains in the Context of Blood Contamination, and Other IgA- and IgM-Related Cerebrospinal Fluid Disease Pattern
Cells 2021, 10(3), 616; https://doi.org/10.3390/cells10030616 - 11 Mar 2021
Cited by 1 | Viewed by 663
Abstract
In this retrospective, monocentric cohort study, we tested if an intrathecal free light chain kappa (FLC-k) synthesis reflects not only an IgG but also IgA and IgM synthesis. We also analysed if FLC-k can help to distinguish between an inflammatory process and a [...] Read more.
In this retrospective, monocentric cohort study, we tested if an intrathecal free light chain kappa (FLC-k) synthesis reflects not only an IgG but also IgA and IgM synthesis. We also analysed if FLC-k can help to distinguish between an inflammatory process and a blood contamination of cerebrospinal fluid (CSF). A total of 296 patient samples were identified and acquired from patients of the department of Neurology, University Medicine Greifswald (Germany). FLC-k were analysed in paired CSF and serum samples using the Siemens FLC-k kit. To determine an intrathecal FLC-k and immunoglobulin (Ig) A/-M-synthesis we analysed CSF/serum quotients in quotient diagrams, according to Reiber et al. Patient samples were grouped into three cohorts: cohort I (n = 41), intrathecal IgA and/or IgM synthesis; cohort II (n = 16), artificial blood contamination; and the control group (n = 239), no intrathecal immunoglobulin synthesis. None of the samples had intrathecal IgG synthesis, as evaluated with quotient diagrams or oligoclonal band analysis. In cohort I, 98% of patient samples presented an intrathecal synthesis of FLC-k. In cohort II, all patients lacked intrathecal FLC-k synthesis. In the control group, 6.5% presented an intrathecal synthesis of FLC-k. The data support the concept that an intrathecal FLC-k synthesis is independent of the antibody class produced. In patients with an artificial intrathecal Ig synthesis due to blood contamination, FLC-k synthesis is lacking. Thus, additional determination of FLC-k in quotient diagrams helps to discriminate an inflammatory process from a blood contamination of CSF. Full article
(This article belongs to the Special Issue Novel Insights on Cerebrospinal Fluid Research)
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Article
Tick-Borne Encephalitis: A Differential Pattern of Intrathecal Humoral Immune Response and Inflammatory Cell Composition Compared with Other Viral CNS Infections
Cells 2020, 9(10), 2169; https://doi.org/10.3390/cells9102169 - 25 Sep 2020
Viewed by 646
Abstract
To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and [...] Read more.
To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and VZV-I was carried out, fulfilling the following criteria: (1) clinical signs of encephalitis and/or meningitis, (2) complete CSF analysis and confirmed viral etiology by either PCR or antibody testing in CSF, (3) hospitalized patients, and (4) available brain magnetic resonance imaging (MRI). Fifty-nine patients with 118 CSF/serum pairs were included. These comprised 21 with TBE (35 CSF/serum pairs), 20 (40 CSF/serum pairs) with HSV-I, and 18 (43 CSF/serum pairs) with VZV-I. In contrast to HSV-I and VZV-I, CSF cell differentiation in TBE showed more often an increased (>20%) proportion of granulocytes (p < 0.01) and a more frequent quantitative intrathecal IgM synthesis (p = 0.001 and p < 0.01, respectively), while the second was even more pronounced when follow-up CSF analyses were included (p < 0.001). CSF findings help to distinguish TBE from other viral infections. In cases with CSF pleocytosis and a positive history for a stay in or near an endemic area, TBE antibodies in CSF and serum should be determined, especially if granulocytes in CSF cell differentiation and/or an intrathecal IgM synthesis is present. Full article
(This article belongs to the Special Issue Novel Insights on Cerebrospinal Fluid Research)
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Review

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Review
The Increasing Role of Kappa Free Light Chains in the Diagnosis of Multiple Sclerosis
Cells 2021, 10(11), 3056; https://doi.org/10.3390/cells10113056 - 06 Nov 2021
Viewed by 312
Abstract
Free light chains (FLC) are a promising biomarker to detect intrathecal inflammation in patients with inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). The diagnostic use of this biomarker, in particular the kappa isoform of FLC (“KFLC”), has been investigated for [...] Read more.
Free light chains (FLC) are a promising biomarker to detect intrathecal inflammation in patients with inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). The diagnostic use of this biomarker, in particular the kappa isoform of FLC (“KFLC”), has been investigated for more than 40 years. Based on an extensive literature review, we found that an agreement on the correct method for evaluating KFLC concentrations has not yet been reached. KFLC indices with varying cut-off values and blood-CSF-barrier (QAlbumin) related non-linear formulas for KFLC interpretation have been investigated in several studies. All approaches revealed high diagnostic sensitivity and specificity compared with the oligoclonal bands, which are considered the gold standard for the detection of intrathecally synthesized immunoglobulins. Measurement of KFLC is fully automated, rater-independent, and has been shown to be stable against most pre-analytic influencing factors. In conclusion, the determination of KFLC represents a promising diagnostic approach to show intrathecal inflammation in neuroinflammatory diseases. Multicenter studies are needed to show the diagnostic sensitivity and specificity of KFLC in MS by using the latest McDonald criteria and appropriate, as well as standardized, cut-off values for KFLC concentrations, preferably considering non-linear formulas such as Reiber’s diagram. Full article
(This article belongs to the Special Issue Novel Insights on Cerebrospinal Fluid Research)

Other

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Opinion
Automated Analysis of Cerebrospinal Fluid Cells Using Commercially Available Blood Cell Analysis Devices—A Critical Appraisal
Cells 2021, 10(5), 1232; https://doi.org/10.3390/cells10051232 - 18 May 2021
Viewed by 569
Abstract
The analysis of cells in the cerebrospinal fluid (CSF) is a routine procedure that is usually performed manually using the Fuchs–Rosenthal chamber and cell microscopy for cell counting and differentiation. In order to reduce the requirement for manual assessment, automated analyses by devices [...] Read more.
The analysis of cells in the cerebrospinal fluid (CSF) is a routine procedure that is usually performed manually using the Fuchs–Rosenthal chamber and cell microscopy for cell counting and differentiation. In order to reduce the requirement for manual assessment, automated analyses by devices mainly used for blood cell analysis have been also used for CSF samples. Here, we summarize the current state of investigations using these automated devices and critically review their limitations. Despite technical improvements, the lower limit for reliable leukocyte counts in the CSF is still at approximately 20 cells/µL, to be validated depending on the device. Since the critical range for clinical decisions is in the range of 5–30 cells/µL this implies that cell numbers < 30/µL require a manual confirmation. Moreover, the lower limit of reliable erythrocyte detection by automated devices is at approximately 1000/µL. However, even low erythrocyte numbers may be of clinical importance. In contrast, heavily hemorrhagic samples from neurosurgery may be counted automatically at an acceptable precision more quickly. Finally, cell differentiation by automated devices provides only a rough orientation for lymphocytes, granulocytes and monocytes. Other diagnostically important cell types such as tumor cells, siderophages, blasts and others are not reliably detected. Thus, although the automation may give a gross estimate sufficient for the emergency room situation, each CSF requires a manual microscopy for cytological evaluation for the final report. In conclusion, although automated analysis of CSF cells may provide a first orientation of the cell profile in an individual sample, an additional manual cell count and a microscopic cytology are still required and represent the gold standard. Full article
(This article belongs to the Special Issue Novel Insights on Cerebrospinal Fluid Research)
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