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Cerebrospinal Fluid Biomarkers in Clinical Diagnostics
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Cerebrospinal Fluid Biomarkers in Clinical Diagnostics

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (20 April 2022) | Viewed by 4764

Special Issue Editor

Dr. Giulia Bivona

E-Mail Website
Guest Editor
Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
Interests: laboratory medicine; vitamin D; biomarkers; neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Interest in cerebrospinal fluid (CSF) samples has been sparked by the fact that several CSF biomarkers can be measured in clinical practice to identify specific diseases. A key example is represented by Alzheimer’s disease (AD), whose diagnosis takes advantage of the determination of CSF Abeta-40, Abeta-42, the Abeta 42/40 ratio, tTau and pTau. Beyond AD, other neurodegenerative diseases, including motor neuron disease (MND), can benefit from CSF biomarker measurements, such as of neurofilament light chain in amyotrophic lateral sclerosis (ALS). Besides well-established biomarkers, the CSF levels of many molecules have been studied in various diseases, including brain cancer, neurodevelopmental disorders and psychiatric illnesses. However, their clinical usefulness remains unproven, mainly due to a lack of evidence. Before entering clinical practice, a biomarker needs an evaluation and validation process, consisting of rigorous studies, faultless methods and homogeneous features. The aim of this Special Issue is to collect original articles and reviews clarifying which biomarkers can influence clinicians in selecting, ruling out and guiding therapy in neurological and neuropsychiatric diseases, and identifying candidate molecules for potential use in clinical practice in the near future.

Dr. Giulia Bivona
Guest Editor

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Keywords

  • Cerebrospinal fluid (CSF)
  • Neurodegeneration
  • Biomarkers
  • Neurological diseases
  • Psychiatric illness
  • Validation
  • Clinical practice
  • Neurofilament
  • Alzheimer’s disease

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Published Papers (3 papers)

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Research

7 pages, 599 KiB  
Article
Evaluation of Alpha-Synuclein Cerebrospinal Fluid Levels in Several Neurological Disorders
by Luisa Agnello, Bruna Lo Sasso, Matteo Vidali, Concetta Scazzone, Caterina Maria Gambino, Tommaso Piccoli, Giulia Bivona, Anna Maria Ciaccio, Rosaria Vincenza Giglio, Vincenzo La Bella and Marcello Ciaccio
J. Clin. Med. 2022, 11(11), 3139; https://doi.org/10.3390/jcm11113139 - 31 May 2022
Cited by 7 | Viewed by 2272
Abstract
(1) Background: Alpha-synuclein (α-syn) is a presynaptic neuronal protein that regulates several neuronal functions. In recent decades, the role of α-syn as a biomarker of neurodegenerative diseases has been explored, especially in synucleinopathies. However, only a few studies have assessed its role as [...] Read more.
(1) Background: Alpha-synuclein (α-syn) is a presynaptic neuronal protein that regulates several neuronal functions. In recent decades, the role of α-syn as a biomarker of neurodegenerative diseases has been explored, especially in synucleinopathies. However, only a few studies have assessed its role as biomarker in other neurological disorders. The aim of the study was to evaluate cerebrospinal fluid (CSF) α-syn levels in several neurological disorders; (2) Methods: We measured CSF α-syn levels by a commercial ELISA kit in 158 patients classified in the following group: controls, Alzheimer’s Disease (AD), cerebrovascular diseases, inflammatory central nervous system diseases, other neurological diseases, Parkinson’s Disease (PD), and peripheral neuropathy; (3) Results: Patients with PD showed the lowest and patients with AD the highest levels of CSF α-syn (1372 vs. 2912 pg/mL, respectively, p < 0.001). In AD patients, α-syn levels were significantly associated with tau proteins; (4) Conclusions: α-syn could represent a biomarker of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid Biomarkers in Clinical Diagnostics)
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18 pages, 2566 KiB  
Article
Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses
by Ji Hye Im, Tae Hoon Kim, Kyue-Yim Lee, Ho-Shin Gwak, Weiwei Lin, Jong Bae Park, Jong Heon Kim, Byong Chul Yoo, Seong-Min Park, Ji-Woong Kwon, Sang Hoon Shin and Heon Yoo
J. Clin. Med. 2021, 10(21), 4860; https://doi.org/10.3390/jcm10214860 - 22 Oct 2021
Cited by 6 | Viewed by 2023
Abstract
The diagnosis of leptomeningeal metastasis (LM) is often difficult due to the paucity of cancer cells in cerebrospinal fluid (CSF) and nonspecific findings on neuroimaging. Investigations of extracellular microRNAs (miRNAs) in CSF could be used for both the diagnosis and study of LM [...] Read more.
The diagnosis of leptomeningeal metastasis (LM) is often difficult due to the paucity of cancer cells in cerebrospinal fluid (CSF) and nonspecific findings on neuroimaging. Investigations of extracellular microRNAs (miRNAs) in CSF could be used for both the diagnosis and study of LM pathogenesis because they reflect the activity of disseminating cancer cells. We isolated CSF extracellular miRNAs from patients (n = 65) of different central nervous system tumor statuses, including cancer control, healthy control, LM, brain metastasis (BM), and primary brain tumor (BT) groups, and performed miRNA microarrays. In unsupervised clustering analyses, all LM and two BM samples showed unique profiles. Among 30 miRNAs identified for LM-specific biomarkers via a Prediction Analysis of Microarrays, miR-335-5p and miR-34b-3p were confirmed in both the discovery and validation samples (n = 23). Next, we performed a significance analysis of the microarray (SAM) to extract discriminative miRNA profiles of two selected CSF groups, with LM samples revealing a greater number of discriminative miRNAs than BM and BT samples compared to controls. Using SAM comparisons between LM and BM samples, we identified 30 upregulated and 6 downregulated LM miRNAs. To reduce bias from different primary cancers, we performed a subset analysis with primary non-small cell lung cancer, and 12 of 13 upregulated miRNAs in LM vs. BM belonged to the upregulated miRNAs in LM. We identified possible target genes and their biological processes that could be affected by LM discriminative miRNAs in NSCLC using the gene ontology database. In conclusion, we identified a unique extracellular miRNA profile in LM CSF that was different from BM, suggesting the use of miRNAs as LM biomarkers in studies of LM pathogenesis. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid Biomarkers in Clinical Diagnostics)
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9 pages, 499 KiB  
Article
Free Immunoglobulin Light Chains in Patients with Tick-Borne Encephalitis: Before and after Treatment
by Monika Gudowska-Sawczuk, Piotr Czupryna, Anna Moniuszko-Malinowska, Sławomir Pancewicz and Barbara Mroczko
J. Clin. Med. 2021, 10(13), 2922; https://doi.org/10.3390/jcm10132922 - 29 Jun 2021
Cited by 13 | Viewed by 1968
Abstract
Background: Tick-borne encephalitis (TBE) is inflammation of the central nervous system (CNS) caused by a viral infection which may be associated with increased synthesis of immunoglobulins. It can lead to inter alia, breakdown of the blood-brain barrier (BBB), or even death and, unfortunately, [...] Read more.
Background: Tick-borne encephalitis (TBE) is inflammation of the central nervous system (CNS) caused by a viral infection which may be associated with increased synthesis of immunoglobulins. It can lead to inter alia, breakdown of the blood-brain barrier (BBB), or even death and, unfortunately, treatment is only symptomatic. Therefore, the aim of the present study was assessment of the concentrations of free light chains (FLC) kappa (κ) and lambda (λ in the cerebrospinal fluid (CSF) and serum of patients with TBE. Methods: A total of 58 cerebrospinal fluid and serum sample pairs were analyzed. Samples were collected from patients with TBE before and after treatment. FLC were measured using the turbidimetric method. The values of κIgG-index, λIgG-index, κFLC-index and λFLC-index were calculated using relevant formulas. Results: Pre-treatment serum λFLC concentrations were higher in comparison to post-treatment levels. Moreover, it was observed that CSF λFLC, TBEV IgM, TBEV IgG, and serum TBEV IgG, as well as the values of λFLC-index, κFLC-index, and λIgG-index were elevated after treatment. In the total study group, the concentrations of CSF κFLC and λFLC, and values of four indexes: κFLC-index, λFLC-index, κIgG-index, and λIgG-index correlated with each other and with CSF TBEV IgM and IgG antibodies. The CSF level of TBEV IgG was also associated with serum IgG TBEV and CSF IgM TBEV antibodies. Additionally, serum κFLC correlated with serum and CSF λFLC. Conclusion: This is the first study that demonstrates statistically significant differences in serum and CSF λFLC, as well as in the calculated values of three algorithms: λIgG-index, κFLC-index, and λIgG-index prior to and following treatment of TBE. Our findings may indicate that these differences reflect the intrathecal synthesis of immunoglobulins and increased permeability of BBB in patients with TBE. Moreover, it could provide the basis for developing new therapeutic strategies. Full article
(This article belongs to the Special Issue Cerebrospinal Fluid Biomarkers in Clinical Diagnostics)
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