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First published on September 24, 2007, doi:10.1177/1352458507082061

Multiple Sclerosis 2008;14:59.

A more recent version of this article appeared on January 1, 2008

Article

Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis

Konrad Rejdak1*, A. Petzold2, Z. Stelmasiak1, and Gavin Giovannoni3

1 Department of Neurology, Medical University of Lublin, Lublin, Poland
2 Department of Neuroinflammation, Institute of Neurology, UCL, London, UK
3 Institute of Cell and Molecular Science, Queen Mary University of London and Department of Neurology, Medical Research Center, Polish Acadamy of Sciences, Warsaw, Poland

* To whom correspondence should be addressed.


  Abstract

This study investigated the cerebrospinal fluid (CSF) levels of ferritin, S100B as biomarkers for glial activation and NfHSM135 – a biomarker of axonal damage – in relation to nitric oxide (NO) metabolites: nitrate and nitrite (NOx) during acute multiple sclerosis (MS) relapse. Thirty-four relapsing–remitting MS (RR-MS) patients during acute relapse and 12 controls were enrolled. Patients were assessed on Expanded Disability Status Scale (EDSS) and underwent lumbar puncture within two weeks following relapse. Twenty patients were available for further follow-up and were assessed on EDSS 6–8 weeks since the relapse onset. The CSF NOx (P<0.0001), NfHSM135 (P=0.01) and S100B (P=0.009) but not ferritin (P>0.05) were significantly raised in MS group. There was a significant correlation between CSF ferritin and S100B in RR-MS group (P=0.004). CSF NOx did not correlate with S100B and ferritin in study groups. RR-MS patients with detectable NfHSM135 levels had higher NOx compared with subjects having undetectable NfHSM135 (P=0.03). In the follow-up study, raised baseline levels of NOx (P=0.016) or NfHSM135 (P=0.04) inversely correlated with the clinical recovery grade expressed as relative EDSS change between baseline and follow-up. In conclusion, NO metabolites were increased and because of their correlation with a biomarker of axonal degeneration (neurofilaments) and a measure for clinical disability (EDSS), relapse-related nitrosative stress is likely to be relevant to the development of sustained disability in an individual patient.

Key Words: cerebrospinal fluid, ferritin, multiple sclerosis, neurofilament, nitric oxide, NOx, S100B


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