NO_x (Nitrite/Nitrate) in Cerebral Spinal Fluids Obtained from Patients with Influenza-Associated Encephalopathy

Abstract

It has become evident that the number of patients with a new type of influenza-associated encephalopathy is increasing in Japan. Nitric oxide (NO), a simple free radical gas, elicits a wide range of physiological and pathophysiological effects. We measured the nitrite/nitrate (NO_x) levels in cerebral spinal fluid obtained from patients with influenza-associated encephalopathy in order to evaluate the correlation between the NO production and the process of influenza-associated encephalopathy. Fifteen children were enrolled, aged from 1 to 9 years. As control we used 14 cerebral spinal fluids obtained from patients with urinary tract infection, respiratory infection or mumps meningitis without any sequela. NO₃ in influenza-associated encephalopathy was significantly higher than that of control group. On the other hand NO₂ was not significantly higher than that of control group. In particular, 4 out of 5 fatal cases revealed high NO₂ or NO_3. One case having normal levels in NO₂ and NO₃ showed that NH₃ was high. These results revealed that NO plays a role in influenza-associated encephalopathy through indirect effects of NO.

Influenza virus - encephalopathy - nitric oxide - central nervous system - cerebral spinal fluids

References

• 1 Okabe N, Yamashita K, Taniguchi K. et al . Influenza surveillance system of Japan and acute encephalitis and encephalopathy in the influenza season.  Pediatr International. 2000;  42 187-191
• 2 Morishima T, Togashi T, Yokota S. et al . Encephalitis and encephalopathy associated with influenza epidemic in Japan.  Clin Infect Dis. 2002;  35 512-517
• 3 Ichiyama T, Nishikawa M, Yoshitomi T, Hayashi T, Furukawa S. Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures.  Neurology. 1998;  50 407-411
• 4 Yoshikawa H, Yamazaki S, Watanabe T, Abe T. Study on influenza-associated encephalitis/encephalopathy in children during the 1997 to 2001 influenza seasons.  J Child Neurol. 2001;  16 885-890
• 5 Kawashima H, Watanabe Y, Ichiyama T, Mizuguchi M, Yamada N, Kashiwagi Y. et al . High concentration of serum NO_x (nitrite/nitrate) obtained from patients with influenza-associated encephalopathy.  Pediatr International. 2002;  44 705-707
• 6 Yokota S. Feature articles: influenza virus infection involving the central nervous system.  Pediatrics International. 2000;  42 186
• 7 Matsuoka H, Watanabe Y, Isshiki A. Increased production of nitric oxide metabolites in the hippocampus under isoflurane anesthesia in rats.  Eur J Anasthesiol. 1999;  16 216-224
• 8 Davis K L, Martin E, Turko I V. et al . Novel effects of nitric oxide.  Annu Rev Pharmacol. 2001;  41 203-236
• 9 Furth A M, Seijimonsbergen E M, Groenveld P HH, Furth R, Langermans J AM. Levels of nitric oxide correlate with high levels of tumor necrosing factor α in cerebrospinal fluid samples from children with bacterial meningitis.  Clin Infect Dis. 1996;  22 876-878
• 10 Tsukahara H, Haruta T, Hata I, Mayumi M. Nitric oxide in septic and aseptic meningitis in children.  Scan J Clin Lab Invest. 1998;  58 73-80
• 11 Tureen J. Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide.  J Clin Invest. 1995;  95 1086-1091