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
concomitant with 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.
Isoprostanes are prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidation of essential fatty acids (primarily arachidonic acid) without the direct action of cyclooxygenase
(COX) enzyme. These were higher in MSers and the less isoprostanes they
had the more loss of brain tissue there was as assessed by MRI brain
volume and NAA which is a nerve molecule and acoording to this study
were more likely to suffer a relapse.