scholarly journals Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mária Péter ◽  
Wanda Török ◽  
Anna Petrovics-Balog ◽  
László Vígh ◽  
László Vécsei ◽  
...  

Abstract Multiple sclerosis (MS) and Guillain–Barré syndrome (GBS) are demyelinating disorders affecting the central nervous system and peripheral nervous system (PNS), respectively. Cerebrospinal fluid (CSF) is one of the most valuable sources of diagnostic biomarkers in neurological diseases. In the present study high sensitivity shotgun mass spectrometry was used to characterise the CSF lipidome of patients with MS, GBS and controls with non-demyelinating diseases. The quantification of 222 CSF lipid molecular species revealed characteristic changes in the absolute and relative lipid concentrations in MS and GBS compared to the controls. For the GBS group, the fourfold elevation in the total lipid content was a discriminatory and a newly identified feature of PNS demyelination. In contrast, in MS, the accumulation of the myelin-derived cerebrosides represented a specific feature of demyelination. As a common feature of demyelination, we identified upregulated levels of lipid metabolic intermediates. We found strong positive correlation between total protein content and lipid concentrations in both diseases. By exploring the CSF lipidome we demonstrate usefulness of broad-range shotgun lipidomic analysis as a fast and reliable method of biomarker discovery in patients with demyelinating neurological disorders that might be a valuable diagnostic complement to existing examinations.

2020 ◽  
Vol 21 (8) ◽  
pp. 2927
Author(s):  
Monika Gudowska-Sawczuk ◽  
Barbara Mroczko

Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.


2021 ◽  
pp. 135245852110487
Author(s):  
Ki Hoon Kim ◽  
Su-Hyun Kim ◽  
Na Young Park ◽  
Jae-Won Hyun ◽  
Ho Jin Kim

The prevalence of cerebrospinal fluid–specific oligoclonal bands (CSF-OCBs) was reported to be low in Asian people with multiple sclerosis (pwMS) compared to that in Western pwMS. It is yet to be determined whether it is a genuine feature of Asian pwMS or a misapprehension owing to past mis-classification of MS-mimicking diseases as MS. We aimed to reappraise the prevalence of CSF-OCBs in Korean pwMS after carefully excluding other central nervous system-inflammatory demyelinating diseases since 2017. Among 88 subjects, 78 (88.6%) were positive for CSF-OCBs, which suggests the prevalence of CSF-OCBs is not different between Korean and Western pwMS.


2018 ◽  
Vol 56 (4) ◽  
pp. 609-613 ◽  
Author(s):  
Estefania Valencia-Vera ◽  
Ana Martinez-Escribano Garcia-Ripoll ◽  
Alfredo Enguix ◽  
Carmen Abalos-Garcia ◽  
Maria Jesus Segovia-Cuevas

Abstract Background: The determination of κ free light chains (KFLC) in cerebrospinal fluid (CSF) by nephelometry is a feasible alternative to immunoglobulin G oligoclonal bands (OCB) in the evaluation of intrathecal synthesis of immunoglobulin in multiple sclerosis (MS) and other demyelinating diseases. The aim of this study was to assess the diagnostic value of KFLC and its inclusion in a procedure algorithm along with OCB interpretation. Methods: A cross-sectional study, which included 123 patients with a CSF OCB request, was carried out. Isoelectric focusing followed by immunofixation was used to detect OCB, and nephelometry was used to analyze KFLC. The KFLC index was calculated using CSF/serum quotient of KFLC and albumin. The KFLC index was compared with MS diagnosis to find the optimal cutoff. It was obtained from the receiver operating characteristic (ROC) curves and the Youden method. Results: The CSF KFLC median was 1.66 mg/L in the MS group, whereas in other central nervous system diseases, KFLC showed generally no or only moderate increase in CSF (median 0.10 mg/L). KFLC index showed a significant difference between groups. ROC analysis for CSF KFLC concentration, and KFLC indexes were 91.88% and 93.94%, respectively. The best cutoff for the KFLC index was 2.91 for MS diagnosis (sensitivity: 83.78%; specificity: 85.88%). The proposed algorithm showed high sensitivity (89.19%) and specificity (84.71%). Conclusions: KFLC determination is rapid and automatized, but it has no higher sensitivity and specificity than OCB in MS diagnosis. Nevertheless, when used in screening, it could reduce the number of manual OCB tests.


2020 ◽  
Vol 10 (6) ◽  
pp. 345 ◽  
Author(s):  
Marina Kleopatra Boziki ◽  
Alexios-Fotios A. Mentis ◽  
Maria Shumilina ◽  
Gleb Makshakov ◽  
Evgeniy Evdoshenko ◽  
...  

In the frame of the coronavirus disease 2019 (COVID-19) pandemic, recent reports on SARS-CoV-2 potential neuroinvasion placed neurologists on increased alertness in order to assess early neurological manifestations and their potentially prognostic value for the COVID-19 disease. Moreover, the management of chronic neurological diseases, such as Multiple Sclerosis (MS), underwent guided modifications, such as an Extended Interval Dose (EID) of Disease-Modifying Treatment (DMT) administration, in order to minimize patients’ exposure to the health system, thus reducing the risk of SARS-CoV-2 infection. In this review, we summarize existing evidence of key immune pathways that the SARS-CoV-2 modifies during COVID-19 and the relevant implication for MS and other autoimmune diseases with associated demyelination (such as Systemic lupus erythematosus and Antiphospholipid syndrome), including the context of potential neuroinvasion by SARS-Cov-2 and the alterations that DMT induces to the immune system. Moreover we hereby aim to provide an overview of the possible consequences that COVID-19 may carry for the Central Nervous System (CNS) in People with MS (PwMS) and other demyelinating diseases, which are likely to pose challenges for treating Neurologists with respect to the long-term disease management of these diseases.


2013 ◽  
Vol 71 (9B) ◽  
pp. 685-688 ◽  
Author(s):  
Sandro Luiz de Andrade Matas ◽  
Felipe von Glehn ◽  
Gustavo Bruniera Peres Fernandes ◽  
Carlos Augusto Senne Soares

The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS), neuromyelitis optic (NMO) and acute disseminated encephalomyelitis (ADEM). The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the probability of Clinical Isolated Syndrome turn into multiple sclerosis.


2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolo’ Bruschi ◽  
Giacomo Boffa ◽  
Matilde Inglese

Abstract Magnetic resonance imaging (MRI) is essential for the early diagnosis of multiple sclerosis (MS), for investigating the disease pathophysiology, and for discriminating MS from other neurological diseases. Ultra-high-field strength (7-T) MRI provides a new tool for studying MS and other demyelinating diseases both in research and in clinical settings. We present an overview of 7-T MRI application in MS focusing on increased sensitivity and specificity for lesion detection and characterisation in the brain and spinal cord, central vein sign identification, and leptomeningeal enhancement detection. We also discuss the role of 7-T MRI in improving our understanding of MS pathophysiology with the aid of metabolic imaging. In addition, we present 7-T MRI applications in other demyelinating diseases. 7-T MRI allows better detection of the anatomical, pathological, and functional features of MS, thus improving our understanding of MS pathology in vivo. 7-T MRI also represents a potential tool for earlier and more accurate diagnosis.


2017 ◽  
Vol 6 (1) ◽  
pp. 1369805 ◽  
Author(s):  
Joanne L. Welton ◽  
Samantha Loveless ◽  
Timothy Stone ◽  
Chris von Ruhland ◽  
Neil P. Robertson ◽  
...  

2012 ◽  
Vol 19 (7) ◽  
pp. 863-870 ◽  
Author(s):  
M Lindén ◽  
M Khademi ◽  
I Lima Bomfim ◽  
F Piehl ◽  
M Jagodic ◽  
...  

Background: The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing–remitting MS (RRMS). Objective: To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients. Methods: We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND). Results: Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13. Conclusion: Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort.


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