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

Background. Among several pathogenic mechanisms of axonal damage in Multiple Sclerosis (MS), oxidative stress (OS) plays a substantial role. Oxygen free radicals lead to lipid peroxidation and subsequent formation of Isoprostanes (IsoP), which can be quantified in the cerebrospinal fluids (CSF) as a reliable index of intrathecal OS. F2-IsoP were shown to be higher in MS patients as compared to controls, and they were proposed as index of neural damage. Although axonal damage is present in patients soon after the first clinical episode suggestive of MS, so far no study evaluated IsoP levels in patients at this stage. Objective: a) to compare F2-IsoP in CSF of MS patients at the disease-onset with those of healthy controls; b) to correlate F2-IsoP levels with Magnetic Resonance Imaging (MRI) measures of brain damage, such as T2-lesions, Gadolinium-enhancing lesions, spectroscopic values and brain atrophy; c) to assess the F2-IsoP role in detecting patients at higher risk of developing relapses. Methods: Thirty-nine patients with a first clinical attack suggestive of MS underwent neurological examination, lumbar puncture and conventional/spectroscopic MRI. Patients were followed-up for 2 years. Results. CSF F2-IsoP levels were higher in patients than in 22 controls (mean[SD] 123.4[185.8] vs 4.5[2.9]pg/ml; p<0.0001). IsoP were inversely related to normalised brain volume (NBV) (p=0.04) and to NAA/Cho (p=0.01). Over 2 years, clinical relapses occurred more frequently in patients with higher baseline IsoP levels than in those with lower IsoP (61% vs 27%; p=0.04). Conclusions. CSF F2-IsoP might be a potential biomarker of tissue damage in MS.