J Neurol (2003) 250 : 588 – 592 DOI 10.1007/s00415-003-1041-0 ORIGINAL COMMUNICATION G. Acar F. I ˙ diman E. I ˙ diman G. Kırkalı H. Çakmakçı S. Özakbas¸ Nitric oxide as an activity marker in multiple sclerosis JON 1041 Introduction Multiple sclerosis (MS) is the most common chronic de- myelinating disease of the central nervous system (CNS) characterized by chronic inflammation of the white matter. Although not a single etiological factor has been identified, there is evidence of an important role of au- toimmunity in the pathogenesis of MS [23, 26]. Mono- cytes and macrophages play key roles during the de- myelination process in MS. Following the infiltration of monocytes, macrophages and T lymphocytes into the brain parenchyma via a defective blood-brain barrier, endogenous glia are activated and subsequently myelin ■ Abstract Nitric oxide (NO) mol- ecules have one of the most impor- tant roles in the pathogenesis of multiple sclerosis (MS). It has been stated that a continuous and high Received: 29 August 2002 Received in revised form: 19 November 2002 Accepted: 26 November 2002 G. Acar · F. I ˙ diman · E. I ˙ diman · S.Özakbas¸ Department of Neurology Dokuz Eylül University School of Medicine Izmir, Turkey G. Kırkalı Department of Biochemistry Dokuz Eylül University School of Medicine Izmir, Turkey H. Çakmakçı Department of Radiodiagnostics Dokuz Eylül University School of Medicine Izmir, Turkey Göksemin Acar, M. D. () 1738.Sok. No 140 4/4 Bostanlı Izmir, Turkey Tel:. + 90-5 32/3 81 75 78 E-Mail: goksemind@yahoo.com concentration of NO metabolites in CSF and in the serum of MS pa- tients in relapse may cause toxic damage to myelin and oligoden- droglia. The aim of this study was to investigate whether NO is a marker of disease activity and is correlated with other disease activ- ity markers such as active lesions on brain magnetic resonance imag- ing (MRI) and increased im- munoglobulin G (IgG) index. Cerebrospinal fluid (CSF) and peripheral serum (PS) samples were taken from patients with defi- nite MS (n = 24) during relapse and remission and from control sub- jects (n = 18). The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in CSF and PS. Cranial MRI was car- ried out with triple dose (0,3 mmol/kg) gadolinium and the IgG index was determined. Nitrite and nitrate concentra- tions (NNCs) of CSF were 11.16 ± 8.60 µmol/ml in relapse and 6.72 ± 3.50 µmol/ml in remission, whereas in PS they were 12.89 ± 7.62 µmol/ml during relapse and 12.35 ± 6.62 µmol/ml during remission. In control subjects NNCs in CSF and PS were 7.42 ± 2.81 µmol/ml and 4.37 ± 1.63 µmol/ml respectively. NNCs in CSF during relapse period were significantly higher than those of both remission phase and control subjects (p = 0.000). Al- though serum NNCs did not differ in relapse and remission, they were still higher than normal controls. Validity analysis revealed that NNC measurement in CSF was 71 % spe- cific and 66 % sensitive to disease activity. The most important result was the significant correlation of increased NNCs with the existence of active lesion in cranial MRI and an increase in IgG index (p < 0.05). In conclusion, these results add background data to assist in fur- ther outlining the possible role of NO in the pathogenesis of MS. To- gether with the other markers it may be used as an activity marker in relapses of MS. ■ Key words multiple sclerosis · activity marker · nitric oxide