| Title | CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis. | | Author(s) | Rejdak K, Eikelenboom MJ, Petzold A, Thompson EJ, Stelmasiak Z, Lazeron RH, Barkhof F, Polman CH, Uitdehaag BM, Giovannoni G | | Institution | Department of Neuroinflammation, Institute of Neurology, London, UK. krejdak@europe.com | | Source | Neurology 2004 Oct 26; 63(8):1439-45. | | MeSH | Adult
Aged
Biological Markers
Central Nervous System
Cross-Sectional Studies
Disability Evaluation
Disease Progression
Female
Follow-Up Studies
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis
Neuropsychological Tests
Nitrates
Nitric Oxide
Nitrites
Predictive Value of Tests
Research Support, Non-U.S. Gov't
Up-Regulation
| | Abstract | 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 < or = 6.0; EDSS < or = 4.0; Multiple Sclerosis Severity Score [MSSS] < or = 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15505162 |
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