The cerebrospinal fluid in multiple sclerosis: far beyond the bands

Domingues, Renan Barros; Fernandes, Gustavo Bruniera Peres; Leite, Fernando Brunale Vilela de Moura; Tilbery, Charles Peter; Thomaz, Rodrigo Barbosa; Silva, Gisele Sampaio; Mangueira, Cristóvão Luis Pitangueira; Soares, Carlos Augusto Senne

doi:10.1590/s1679-45082017rw3706

Cited by 17 publications

(14 citation statements)

References 43 publications

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“…[16][17][18][19] For the method to have full clinical potential for OB IgG analysis in CSF, standardisation of laboratory methods and diagnostic criteria is necessary. 20,21 Results of the present study showed high sensitivity of the IEF method (96.6 %) in the examined group of MS patients in this laboratory. Recent studies have shown that the detection of OB in the CSF has a predictive significance for the course of the disease and the progression of disability expressed by EDSS score.…”

Section: Standard Deviationsupporting

confidence: 48%

Prognostic significance of intrathecal oligoclonal immunoglobulin G in multiple sclerosis

Grgić¹,

Dominović-Kovačević²,

Đajić³

et al. 2020

Scripta Medica

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Introduction/Aim: Detection of intrathecal oligoclonal bands of immunoglobulin G (OB IgG), in addition to diagnostic, has a predictive significance in multiple sclerosis (MS). The aim of the study was to determine the prognostic significance of OB IgG and to correlate the presence of OB IgG with the progression of disability in MS patients. Methods: A retrospective-prospective cohort study included 177 MS patients examined at the Centre for MS, Clinic of Neurology, University Clinical Centre of the Republic of Srpska. In all patients, demographic data, clinical parameters, Expanded Disability Status Scale (EDSS) score, isoelectric focusing (IEF) of cerebrospinal fluid (CSF), cyto-biochemical analysis of CSF, evoked potentials (EP) and magnetic resonance (MR) of the head were analysed. MS patients were divided in two groups: with and without intrathecal synthesis of oligoclonal IgG. According to the EDSS determined in both groups, the relation between the degree of functional disability and the presence of OB in the CSF and also with characteristics of the cyto-biochemical profile were analysed. Methods of descriptive and analytical statistics, analysis of variance, chi-square test, Bonferroni's post hoc test, correlation and regression analysis were used in the analysis of the results. Results: In the examined cohort of MS patients, the sensitivity of IEF was 96.6 %. There was a statistically significant association between the detectability of intrathecally synthesised IgG and EDSS score (p = 0.004) so that individuals who do not have intrathecally synthesised IgG had lower EDSS scores. MS patients with a CSF protein concentration > 0.40 g/L were 2.45 times more likely to enter secondary progression and 2.51 times more likely to achieve EDSS 4.0. Conclusion: IEF is a very sensitive diagnostic and prognostic method for MS patients, which indicates a more benign course of MS in patients without oligoclonal bands in the CSF.

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Section: Standard Deviationsupporting

confidence: 48%

Prognostic significance of intrathecal oligoclonal immunoglobulin G in multiple sclerosis

Grgić¹,

Dominović-Kovačević²,

Đajić³

et al. 2020

Scripta Medica

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“…TNF is a pleiotropic cytokine increasingly recognized to regulate important physiological processes not only in the immune system, but also in the brain [ 9 , 10 , 11 ]. Evidence for TNF involvement in MS includes the identification of TNF in astrocytes, microglia, and endothelial cells, preferentially in acute and chronic active MS brain lesions and in the cerebrospinal fluid (CSF) of MS subjects [ 12 , 13 , 14 ]. TNF has a complex, and presumably multifaceted, role in the immunopathogenesis of MS, as suggested by both animal experiments and clinical studies in humans, including the failure of an anti-TNF clinical trial [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Re-Examining the Role of TNF in MS Pathogenesis and Therapy

Fresegna

Bullitta

Musella

et al. 2020

Cells

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Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human and experimental MS have demonstrated the involvement of TNF in various pathological hallmarks of MS, including immune dysregulation, demyelination, synaptopathy and neuroinflammation. However, due to the complexity of TNF signaling, which includes two-ligands (soluble and transmembrane TNF) and two receptors, namely TNF receptor type-1 (TNFR1) and type-2 (TNFR2), and due to its cell- and context-differential expression, targeting the TNF system in MS is an ongoing challenge. This review summarizes the evidence on the pathophysiological role of TNF in MS and in different MS animal models, with a special focus on pharmacological treatment aimed at controlling the dysregulated TNF signaling in this neurological disorder.

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“…The recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. Currently available cerebrospinal fluid (CSF) or serum biomarkers and magnetic resonance imaging (MRI) have limited sensitivity and specificity, and novel biomarkers of CNS inflammation are constantly being assessed [1–3].…”

Section: Introductionmentioning

confidence: 99%

Utility of chemokines CCL2, CXCL8, 10 and 13 and interleukin 6 in the pediatric cohort for the recognition of neuroinflammation and in the context of traditional cerebrospinal fluid neuroinflammatory biomarkers

et al. 2019

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Background The recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. The present study aimed to determine the diagnostic relevance of five selected chemo/cytokines in the recognition of CNS inflammation and in the context of traditional cerebrospinal fluid (CSF) biomarkers (white blood cell [WBC] counts, oligoclonal bands, protein levels, CSF/serum albumin ratios) and clinical diagnoses. Methods C-C and C-X-C motif ligands (CCL2, CXCL8, 10 and 13) and interleukin (IL) 6 levels in the CSF and serum from 37 control and 87 symptomatic children with ten different (mostly noninfectious) inflammatory CNS disorders (16 of which had follow-up samples after recovery) were determined using Luminex multiple bead technology and software. Nonparametric tests were used; p < 0.05 was considered statistically significant. Receiver operating characteristic curves were constructed to analyze controls and 1) all symptomatic samples or 2) symptomatic samples without CSF pleocytosis. Results Compared with the control CSF samples, levels of all investigated chemo/cytokines were increased in symptomatic CSF samples, and only IL-6 remained elevated in recovery samples (p ≤ 0.001). CSF CXCL-13 levels (> 10.9 pg/mL) were the best individual discriminatory criterion to differentiate neuroinflammation (specificity/sensitivity: 97/72% and 97/61% for samples without pleocytosis), followed by CSF WBC counts (specificity/sensitivity: 97/62%). The clinical utility of the remaining CSF chemo/cytokine levels was determined in descending order of sensitivities corresponding to thresholds that ensured 97% specificity for neuroinflammation in samples without pleocytosis (pg/mL; sensitivity %): IL-6 (3.8; 34), CXCL8 (32; 26), CXCL10 (317; 24) and CCL2 (387; 10). Different diagnosis-related patterns of CSF chemo/cytokines were observed. Conclusions The increased CSF level of CXCL13 was the marker with the greatest predictive utility for the general recognition of neuroinflammation among all of the individually investigated biomarkers. The potential clinical utility of chemo/cytokines in the differential diagnosis of neuroinflammatory diseases was identified.

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The cerebrospinal fluid in multiple sclerosis: far beyond the bands

Cited by 17 publications

References 43 publications

Prognostic significance of intrathecal oligoclonal immunoglobulin G in multiple sclerosis

Prognostic significance of intrathecal oligoclonal immunoglobulin G in multiple sclerosis

Re-Examining the Role of TNF in MS Pathogenesis and Therapy

Utility of chemokines CCL2, CXCL8, 10 and 13 and interleukin 6 in the pediatric cohort for the recognition of neuroinflammation and in the context of traditional cerebrospinal fluid neuroinflammatory biomarkers

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