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.