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CSF nitrite and nitrate levels were increased in mildly disabled patients with MS and found to correlate with the volume of Gd-enhanced lesions on MRI. Raised baseline CSF NOx was associated with clinical and MRI progression in MS patients over 3-year follow-up.

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This study investigated the cerebrospinal fluid (CSF) levels of ferritin, S100B as biomarkers for glial activation and NfH(SM135)--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), NfH(SM135) (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 NfH(SM135) levels had higher NOx compared with subjects having undetectable NfH(SM135) (P=0.03). In the follow-up study, raised baseline levels of NOx (P=0.016) or NfH(SM135) (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.