Isoprostanes in clinically isolated syndrome and early multiple sclerosis as biomarkers of tissue damage and predictors of clinical course

Abstract

Background: Isoprostanes (IsoP) are sensitive biomarkers of oxidative stress. Their cerebrospinal-fluid (CSF) level is increased in several neurological conditions, including multiple sclerosis (MS). In particular, in relapsing–remitting MS, IsoP have been proposed as an index of neurodegenerative processes. The mechanisms leading to neuroaxonal damage in MS are not fully understood but oxidative mechanisms play a substantial role. Although axonal loss is present in MS patients since their first clinical symptoms, IsoP levels at this early stage have not been evaluated yet. Objectives: The objectives of this study were (a) to assess IsoP levels in CSF of patients with a first clinical attack suggestive of MS; (b) to correlate IsoP levels with magnetic resonance imaging (MRI) measures of brain damage and (c) to assess IsoP value in predicting disease clinical evolution. Methods: Thirty-nine patients with a first clinical attack suggestive of MS underwent neurological examination, lumbar puncture with IsoP levels quantification and conventional/spectroscopic-MRI. Patients were followed up for 24 months. Results: CSF IsoP levels were higher in patients than controls (mean±standard deviation (SD) 123.4±185.8 vs 4.5±2.9 pg/ml; p<0.0001) and inversely correlated to normalized brain volume ( p=0.04) and N-acetylaspartate/choline (NAA/Cho) ( p=0.01). The risk of experiencing clinical relapses differed according to IsoP level: subjects with levels higher than 95 pg/ml (a cut-off value resulting from ROC analysis) were more likely to relapse than patients with levels equal or lower than 95 pg/ml (59% vs 27% respectively; p=0.03). Conclusions: CSF IsoP might be useful biomarkers of tissue damage in MS with a predictive value of disease course.