CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis.
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.
Rejdak
K
K
Department of Neuroinflammation, Institute of Neurology, London, UK. krejdak@europe.com
Eikelenboom
M J
MJ
Petzold
A
A
Thompson
E J
EJ
Stelmasiak
Z
Z
Lazeron
R H C
RH
Barkhof
F
F
Polman
C H
CH
Uitdehaag
B M J
BM
Giovannoni
G
G
D000328:Adult; D000368:Aged; D015415:Biomarkers; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000523:psychology; D009483:Neuropsychological Tests; D009566:Nitrates / Q000097:blood / Q000134:cerebrospinal fluid*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide