Increased intrathecal nitric oxide formation in multiple sclerosis; cerebrospinal fluid nitrite as activity marker

Nitric oxide is formed from L-arginine by a family of enzymes: nitric oxide synthase (NOS). The inducible nitric oxide synthase is activated by cytoki nes and it has been suggested that activation of the enzyme gives rise to n eurotoxic levels of reactive nitrogen oxides. This enzyme has been shown to be localized in multiple sclerosis (MS) lesions but the role of nitric oxi de formation in the pathogenesis of MS is still unclear. Using capillary el ectrophoresis, we have analysed nitrite and nitrate in cerebrospinal fluid (CSF) and demonstrate increased levels of reactive nitrogen products in 17 patients with MS. The total levels of oxidized nitrogen products were signi ficantly elevated in MS patients when compared with controls. In patients w ith active MS, nitrite levels were significantly increased when compared wi th controls and patients in remission. This is supportive of NOS induction in MS. We suggest that capillary electrophoresis analysis of nitrite and ni trate in CSF could provide a clinically useful way to determine disease act ivity in MS. Eur J Neurol 6:585-590 (C) 1999 Lippincott Williams & Wilkins.