Metabolomics of Cerebrospinal Fluid Amino and Fatty Acids in Early Stages of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative autoimmune disease of the central nervous system (CNS) damaging myelin and axons. Diagnosis is based on the combination of clinical findings, magnetic resonance imaging (MRI) and analysis of cerebrospinal fluid (CSF). Metabolomics is a systematic study that allows us to track amounts of different metabolites in a chosen medium. The aim of this study was to establish metabolomic differences between the cerebrospinal fluid of patients in the early stages of multiple sclerosis and healthy controls, which could potentially serve as markers for predicting disease activity. We collected CSF from 40 patients after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS, and the CSF of 33 controls. Analyses of CSF samples were performed by using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector. Significant changes in concentrations of arginine, histidine, spermidine, glutamate, choline, tyrosine, serine, oleic acid, stearic acid and linoleic acid were observed. More prominently, Expanded Disability Status Scale values significantly correlated with lower concentrations of histidine. We conclude that these metabolites could potentially play a role as a biomarker of disease activity and predict presumable inflammatory changes.

Impaired intestinal permeability in patients with multiple sclerosis.

BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.

Metabolomics of Cerebrospinal Fluid in Multiple Sclerosis Compared With Healthy Controls: A Pilot Study.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) leading to the loss of myelin and axons. Diagnosis is based on clinical findings, MRI, and analysis of cerebrospinal fluid (CSF). CSF is an ultrafiltrate of plasma and reflects inflammatory processes in the CNS. The aim of this study was to perform metabolomics analysis of CSF in patients after the first attack of MS and healthy controls and try to find new specific analytes for MS including those potentially predicting disease activities at the onset. Methods: We collected CSF from 19 patients (16 females, aged 19-55 years) after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS and CSF of 19 controls (16 females, aged 19-50 years). Analyses of CSF samples were provided using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector (TripleTOF 5600, AB Sciex, Canada). Results: Approximately 130 selected analytes were identified, and 30 of them were verified. During the targeted analysis, a significant decrease in arginine and histidine and a less significant decrease in the levels of asparagine, leucine/isoleucine, and tryptophan, together with a significant increase of palmitic acid in the patient group, were found. Conclusion: We observed significant differences in amino and fatty acids in the CSF of newly diagnosed patients with MS in comparison with controls. The most significant changes were observed in levels of arginine, histidine, and palmitic acid that may predict inflammatory disease activity. Further studies are necessary to support these findings as potential biomarkers of MS.

Influence of Hyperglycaemia and CRP on the Need for Mechanical Ventilation in Guillain-Barré Syndrome.

Objectives: Elevated blood glucose and CRP (C-reactive protein) are usually related to a worsened clinical outcome in neurological diseases. This association in Guillain-Barré syndrome (GBS) has been studied rarely. We tried to analyse if hyperglycaemia and CRP at admission may influence the outcome of GBS, including mechanically ventilated (MV) patients. Methods: We retrospectively studied 66 patients (40 males, 19-93 years, average 56 years) without diabetes mellitus and free of corticoid treatment, who fulfilled the clinical criteria for diagnosis of GBS. Hyperglycaemia (the level of fasting plasma glucose, FPG) was defined as blood glucose level >5.59 mmol/L according to our laboratory. CRP >5 mg/L was considered as an abnormally elevated value. Results: At admission, 32 GBS patients (48%) had hyperglycaemia according to FPG level. A severe form of GBS (>4 according to Hughes GBS scale) was observed in 17 patients (26%); and 8 of them (47%) had hyperglycaemia. Fourteen patients (21%) were MV, and in 10 of them (71%) hyperglycaemia was present. CRP was significantly increased in MV patients. The linear model revealed a significant relationship between CRP and glycemia (p = 0.007) in subjects without MV (p = 0.049). In subjects with MV the relationship was not significant (p = 0.2162, NS). Conclusion: In the acute phase of GBS at admission, hyperglycaemia and higher CRP occur relatively frequently, and may be a risk factor for the severity of GBS. Stress hyperglycaemia due to impaired glucose homeostasis could be one explanation for this condition.