Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG bands in patients with clinically isolated and Guillain-Barré syndrome

Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS) pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barré syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB and CIS patients' CSF, MRI, and clinical variables. There was no difference in the proportion of CIS and GB patients with positivity for anti-EBV-specific IgG/IgM OCB. There were no correlations between OCB and analyzed variables, nor were they predictive of a higher disability at 3 years

Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study

Abstract Background: Cerebrospinal fluid (CSF) levels assessment of Aβ1-42 and Tau proteins may be accurate diagnostic biomarkers for the differentiation of preclinical Alzheimer's disease (AD) from age-associated memory impairment, depression and other forms of dementia in patients with mild cognitive impairment (MCI). The aim of our study was to explore the utility of CSF biomarkers in combination with common cognitive markers as predictors for the risk of AD development, and other forms of dementia, and the time to conversion in community patients with MCI. Methods: A group of 71 MCI patients underwent neurological assessment, extended neuropsychological evaluation, routine blood tests, ApoE determination, and lumbar puncture to dose t-tau, p-tau181, Aβ1-42. We investigated baseline CSF and neuropsychological biomarker patterns according to groups stratified with later diagnoses of AD conversion (MCI-AD), other dementia (MCI-NAD) conversion, or clinical stability (sMCI). Results: Baseline Aβ1-42 CSF levels were significantly lower in MCI-AD patients compared to both sMCI and MCI-NAD. Additionally, p-tau181 was higher in the MCI-AD group compared to sMCI. The MCI-AD subgroup analysis confirmed the role of Aβ1-42 in its predictive role of time to conversion: rapid converters had lower Aβ1-42 levels compared to slow converters. Logistic regression and survival analysis further supported the key predictive role of baseline Aβ1-42 for incipient AD and dementia-free survival. Conclusions: Our results confirm the key role of CSF biomarkers in predicting patient conversion from MCI to dementia. The study suggests that CSF biomarkers may also be reliable in a real world clinical setting

SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study

Background: SerpinA1, a serine protease inhibitor, is involved in the modulation of microglial-mediated inflammation in neurodegenerative diseases. We explored SerpinA1 levels in cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients to understand its potential role in the pathogenesis of the disease. Methods: SerpinA1, neurofilament light (NfL) and heavy (NfH) chain, and chitinase-3-like protein-1 (CHI3L1) were determined in CSF and serum of ALS patients (n = 110) and healthy controls (n = 10) (automated next-generation ELISA), and correlated with clinical parameters, after identifying three classes of progressors (fast, intermediate, slow). Biomarker levels were analyzed for diagnostic power and association with progression and survival. Results: SerpinA1serum was significantly decreased in ALS (median: 1032 μg/mL) compared with controls (1343 μg/mL) (p = 0.02). SerpinA1CSF was elevated only in fast progressors (8.6 μg/mL) compared with slow (4.43 μg/mL, p = 0.01) and intermediate (4.42 μg/mL, p = 0.03) progressors. Moreover, SerpinA1CSF correlated with neurofilament and CHI3L1 levels in CSF. Contrarily to SerpinA1CSF , neurofilament and CHI3L1 concentrations in CSF correlated with measures of disease progression in ALS, while SerpinA1serum mildly related with time to generalization (rho = 0.20, p = 0.04). In multivariate analysis, the ratio between serum and CSF SerpinA1 (SerpinA1 ratio) and NfHCSF were independently associated with survival. Conclusions: Higher SerpinA1CSF levels are found in fast progressors, suggesting SerpinA1 is a component of the neuroinflammatory mechanisms acting upon fast-progressing forms of ALS. Both neurofilaments or CHI3L1CSF levels outperformed SerpinA1 at predicting disease progression rate in our cohort, and so the prognostic value of SerpinA1 alone as a measure remains inconclusive

Selenoprotein P Concentrations in the Cerebrospinal Fluid and Serum of Individuals Affected by Amyotrophic Lateral Sclerosis, Mild Cognitive Impairment and Alzheimer’s Dementia

Selenoprotein P, a selenium-transporter protein, has been hypothesized to play a role in the etiology of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's dementia (AD). However, data in humans are scarce and largely confined to autoptic samples. In this case-control study, we determined selenoprotein P concentrations in both the cerebrospinal fluid (CSF) and the serum of 50 individuals diagnosed with ALS, 30 with AD, 54 with mild cognitive impairment (MCI) and of 30 controls, using sandwich enzyme-linked immunosorbent assay (ELISA) methods. We found a positive and generally linear association between CSF and serum selenoprotein P concentrations in all groups. CSF selenoprotein P and biomarkers of neurodegeneration were positively associated in AD, while for MCI, we found an inverted-U-shaped relation. CSF selenoprotein P concentrations were higher in AD and MCI than in ALS and controls, while in serum, the highest concentrations were found in MCI and ALS. Logistic and cubic spline regression analyses showed an inverse association between CSF selenoprotein P levels and ALS risk, and a positive association for AD risk, while an inverted-U-shaped relation with MCI risk emerged. Conversely, serum selenoprotein P concentrations were positively associated with risk of all conditions but only in their lower range. Overall, these findings indicate some abnormalities of selenoprotein P concentrations in both the central nervous system and blood associated with ALS and neurocognitive disorders, though in different directions. These alterations may reflect either phenomena of etiologic relevance or disease-induced alterations of nutritional and metabolic status

Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis

Cerebrospinal fluid (CSF) CXCL13 was shown to correlate with markers of intrathecal inflammation and CSF oligoclonal IgM bands (IgMOB) have been associated with a more severe Multiple Sclerosis (MS) course.We correlated CSF CXCL13 levels with clinical, MRI and CSF parameters, including CSF IgMOB, in 110 Clinically Isolated Syndrome (CIS) patients.CSF CXCL13 levels correlated with CSF cell count, total protein, IgG Index and with the presence of CSF IgGOB and IgMOB.CSF CXCL13 levels ≥. 15.4. pg/ml showed a good positive predictive value and specificity for a MS diagnosis and for a clinical relapse within one year from onset

Kappa Index Versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders

Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID)

Models for the lithium abundances of multiple populations in globular clusters and the possible role of the Big Bang lithium

Globular cluster stars show chemical abundance patterns typical of hot-CNO processing. Lithium is easily destroyed by proton capture in stellar environments, so its abundance may be crucial to discriminate among different models proposed to account for multiple populations. In order to reproduce the observed O-Na anticorrelation and other patterns typical of multiple populations, the formation of second generation stars must occur from the nuclearly processed stellar ejecta, responsible of the chemical anomalies, diluted with pristine gas having the composition of first generation stars. The lithium abundance in the unprocessed gas -which is very likely to be equal to the lithium abundance emerging from the Big Bang- affects the lithium chemical patterns among the cluster stars. This paper focuses on a scenario in which processed gas is provided by asymptotic giant branch (AGB) stars. We examine the predictions of this scenario for the lithium abundances of multiple populations. We study the role of the non-negligible lithium abundance in the ejecta of massive AGB (A(Li)~2), and, at the same time, we explore how our models can constrain the extremely large ---and very model dependent--- lithium yields predicted by recent super--AGB models. We show that the super--AGB yields may be tested by examining the lithium abundances in a large set of blue main sequence stars in wCen and/or NGC2808. In addition, we examine the different model results obtained by assuming for the pristine gas either the Big Bang abundance predicted by the standard models (A(Li)=2.6-2.7), or the abundance detected at the surface of population II stars (A(Li)=2.2-2.3). Once a chemical model is well constrained, the O--Li distribution could perhaps be used to shed light on the primordial lithium abundance

A multicenter study on the diagnostic significance of a single cerebrospinal fluid IgG band

The analysis of paired cerebrospinal fluid (CSF) and serum samples with isolectric focusing (IEF) can yield different patterns which can be of aid in the differential diagnosis of central nervous system (CNS) disorders. Rarely, a single CSF-restricted IgG band, which is not included within these patterns, can be detected in association with inflammatory disorders, multiple sclerosis (MS) above all. However, the diagnostic meaning of this abnormality is still uncertain. The main aim of our multicenter study was to establish the frequency and disease associations of single CSF IgG bands. Differences in the CSF profiles between MS and other diseases, and the follow-up patterns were also evaluated. Medical records of patients who underwent CSF analysis, which included IEF, over a 11.5-year period were retrospectively scrutinized at the participating centers, which used similar IEF techniques. One hundred and fifty-one of 9422 CSF reports (1.6%) showed single CSF-restricted IgG bands. Of the 129 patients with a definite diagnosis, 58.2% had CNS inflammatory-demyelinating diseases (the most frequent being MS: 21.7%), 6.2% tumours, 5.4% inflammatory peripheral nervous system diseases and 30.2% miscellaneous diseases. At follow-up, 3 out of the 10 patients with a repeated CSF analysis had developed an oligoclonal band pattern. Our findings indicate that single CSF IgG bands tend to associate with diseases characterized by the involvement of intrathecal humoral immune responses, and strongly support the notion that this abnormality should be regularly reported, thus alerting clinicians of possible inflammatory disorders of the CNS

Serum IgG against Simian Virus 40 antigens are hampered by high levels of sHLA-G in patients affected by inflammatory neurological diseases, as multiple sclerosis

Background: Many investigators detected the simian polyomavirus SV40 footprints in human brain tumors and neurologic diseases and recently it has been indicated that SV40 seems to be associated with multiple sclerosis (MS) disease. Interestingly, SV40 interacts with human leukocyte antigen (HLA) class I molecules for cell entry. HLA class I antigens, in particular non-classical HLA-G molecules, characterized by an immune-regulatory function, are involved in MS disease, and the levels of these molecules are modified according with the disease status. Objective: We investigated in serum samples, from Italian patients affected by MS, other inflammatory diseases (OIND), non-inflammatory neurological diseases (NIND) and healthy subjects (HS), SV40-antibody and soluble sHLA-G and the association between SV40-prevalence and sHLA-G levels. Methods: ELISA tests were used for SV40-antibodies detection and sHLA-G quantitation in serum samples. Results: The presence of SV40 antibodies was observed in 6 % of patients affected by MS (N = 4/63), 10 % of OIND (N = 8/77) and 15 % of NIND (N = 9/59), which is suggestive of a lower prevalence in respect to HS (22 %, N = 18/83). MS patients are characterized by higher sHLA-G serum levels (13.9 \ub1 0.9 ng/ml; mean \ub1 St. Error) in comparison with OIND (6.7 \ub1 0.8 ng/ml), NIND (2.9 \ub1 0.4 ng/ml) and HS (2.6 \ub1 0.7 ng/ml) subjects. Interestingly, we observed an inverse correlation between SV40 antibody prevalence and sHLA-G serum levels in MS patients. Conclusion: The data obtained showed a low prevalence of SV40 antibodies in MS patients. These results seems to be due to a generalized status of inability to counteract SV40 infection via antibody production. In particular, we hypothesize that SV40 immune-inhibitory direct effect and the presence of high levels of the immune-inhibitory HLA-G molecules could co-operate in impairing B lymphocyte activation towards SV40 specific peptides