Nitric oxide metabolites, nitrates and nitrites in the cerebrospinal fluid in children with west syndrome.
Nitric oxide (NO) has been implicated in the mediation of the neuronal excitotoxic cascade. In order to estimate brain NO production, cerebrospinal fluid (CSF) levels of NO metabolites, nitrates and nitrites (NN(x)) were measured in 31 children with west syndrome (WS) and in 12 controls. There was no age-related change in the NN(x) levels during the first year of life. The mean of the NN(x) levels was significantly higher in patients with WS than in controls (8.43 vs. 5.27 microM; P=0.01). Analysis of the etiological subgroups showed that the patients with a symptomatic etiology of WS had significantly higher NN(x) levels than controls (P<0.005) or than the patients with a cryptogenic etiology. The cryptogenic cases, in turn, did not differ from the controls (P=0.48). Levels of NN(x) were also significantly higher in children with focal brain abnormalities (infarction, atrophy or previous infection) than in those with other abnormalities or with normal neuroradiological findings (P<0.005). No correlation was found between the NN(x) levels and the duration of the symptoms, while paired samples obtained from eight children with WS showed that the NN(x) levels rose significantly (P=0.02) within the first 40 days of symptoms. The levels of NN(x) did not correlate with the CSF levels of neuronal growth factor or with the later decline in mental performance. This study demonstrates that the production of NO can be measured in human epileptic conditions and supports the idea gained from experimental studies that NO is involved in the pathophysiology of epilepsy. However, normal levels of NN(x) in patients with cryptogenic infantile spasms suggest that an increase in NO production be due to the concomitant neuronal damage rather than seizure activity per se. The findings suggest that there are no age-related changes in the NN(x) levels during the first year of life, and that children with symptomatic WS have elevated levels of NN(x), which rise during the first 40 days of symptoms. Although the NN(x) levels cannot be used to estimate the duration of symptoms or to predict the prognosis of mental development, they may support the differentiation of symptomatic from cryptogenic etiologies of WS.
Vanhatalo
S
S
Department of Child Neurology, Children's Hospital, University of Kuopio, Kuopio, Finland. svanhata@helsinki.fi
Riikonen
R
R
D000704:Analysis of Variance; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005387:Finland; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology; D007360:Intelligence; D009566:Nitrates / Q000134:cerebrospinal fluid*; D009569:Nitric Oxide / Q000134:cerebrospinal fluid*; D009573:Nitrites / Q000134:cerebrospinal fluid*; D011581:Psychological Tests; D012016:Reference Values; D013036:Spasms, Infantile / Q000134:cerebrospinal fluid* / Q000503:physiopathology / Q000523:psychology
D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide