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From the Departments of Neuroinflammation (Drs. Rejdak, Petzold, Thompson, Giovannoni) and Neurocritical Care (Dr. Petzold), Institute of Neurology, London, UK; Departments of Neurology (Drs. Eikelenboom, Lazeron, Polman, Uitdehaag) and Radiology (Dr. Barkhof), VU Medical Center, Amsterdam, the Netherlands; Medical Research Center (Dr. Rejdak), Polish Academy of Sciences, Warsaw and Department of Neurology (Drs. Rejdak, Stelmasiak), Medical University, Lublin, Poland.
Address correspondence and reprint requests to Dr. K. Rejdak, Department of Neurology, Medical University in Lublin, 8 Jaczewskiego Str., 20-954 Lublin, Poland; e-mail: krejdak{at}europe.com
Objective: To investigate the relationship of CSF and the serum nitric oxide metabolites nitrite and nitrate (NOx) to disease activity and progression in patients with multiple sclerosis (MS).
Methods: The study was divided into cross-sectional and follow-up. In the cross-sectional study, 20 patients with relapsing–remitting (RR), 21 with secondary progressive (SP), and 10 with primary progressive (PP) MS and 14 control subjects were included. Patients were assessed on clinical (Expanded Disability Status Scale [EDSS], Ambulation Index [AI], 9-Hole Peg Test [9-HPT]) and MRI measurements. In the follow-up study, 34 MS patients from the cross-sectional study agreed to be assessed again after an average of 3.0 ± 0.5 years. NOx was measured using a vanadium-based assay.
Results: In the cross-sectional study, CSF NOx was raised in patients with RR-MS (p = 0.001) and PP-MS (p = 0.02) vs controls. Higher CSF NOx levels were found in patients with mild disability (AI 
6.0; EDSS 4.0; Multiple Sclerosis Severity Score [MSSS] 4.8) vs patients with advanced disease (AI > 6.0 [p = 0.002]; EDSS > 4.0 [p = 0.02]; MSSS > 4.8 [p = 0.01]). In the subgroup of patients having Gd-enhancing MRI lesions (n = 11), correlation between the volume of enhancement and CSF NOx was found (r = 0.74, p = 0.01). In the follow-up study, patients with disability progression had higher baseline CSF NOx levels than those who were stable on EDSS (p = 0.02) or AI (p = 0.03). A positive correlation was found between baseline CSF NOx and the change in MR T2-weighted lesion load (r = 0.4, p = 0.03).
Conclusions: 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.
Received December 10, 2003. Accepted in final form June 15, 2004.
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