Hiroaki Ioi

PRIMARY BIOMARKERS IN CEREBRAL SPINAL FLUID OBTAINED FROM PATIENTS WITH INFLUENZA-ASSOCIATED ENCEPHALOPATHY ANALYZED BY METABOLOMICS

In order to search for the specific biomarkers of patients with influenza-associated encephalopathy this article analyzed all metabolites in cerebrospinal fluid (CSF) by using metabolome analysis. In all metabolites, the peaks of two molecular weights, 246.0092 and 204.0611, were significantly higher than those in other diseases including influenza without convulsion (p < .05). The peak of a molecular weight 228.0247 in all of the patients except one was less than that in other patients. These results indicate that the new metabolites detected in CSF would be primary markers for the diagnosis of influenza-associated encephalopathy.

Classification of acute encephalopathy in respiratory syncytial virus infection

Infection with respiratory syncytial virus (RSV) is known to be associated with central nervous system symptoms such as convulsions. We investigated cytokines, nitrogen oxide (NO)x, and the viral genome in cerebrospinal fluid (CSF) obtained from children with RSV infection-related convulsions or central nervous symptoms and compared the data with type of encephalopathy. Of nine patients enrolled (six boys and three girls; aged 10 days–3 years), one metabolic error, five excitotoxicity, one cytokine storm, and two hypoxia cases were found. The patients presented with unilateral convulsions, generalized convulsions, and convulsions following cardiopulmonary arrest, apnea, and nuchal rigidity. In all patients, a rapid check for RSV of nasal fluid was positive. The RSV genome (subgroup A) was detected in the CSF of five of the nine patients; two patients with hypoxic encephalopathy were negative for the RSV genome. The CSF interleukin (IL)-6 levels were high only in patients with the excitotoxicity and cytokine storm type of encephalopathy. NOx levels were high in all the subject cases. In the excitotoxicity type, NOx levels were significantly higher than those in the control and other groups. NOx level may become an important parameter for the diagnosis and classification of acute encephalopathy in RSV. Strategies to treat each type of encephalopathy, targeting cytokines and free radicals, should be established.

Cerebrospinal fluid analysis in children with seizures from respiratory syncytial virus infection

We report 3 cases of respiratory syncytial virus infection-associated seizures; their abnormalities of cerebrospinal fluid (increased interleukin-6 and positive for virus by highly sensitive assay) were documented. These data revealed that neurological involvement might be caused by a direct invasion.

High production of interleukin‐10 and interferon‐γ in influenza‐associated MERS in the early phase

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) occurs in various diseases and pathologies, and the clinical symptoms are not consistent with the impaired region. The mechanism of the region specificity is unclear. We investigated the cytokine profiling in cerebrospinal fluid (CSF) and serum obtained from a child with MERS during influenza infection, and compared them with those of serious another serious type of influenza‐associated encephalopathy. There was no elevation of Interleukin (IL)‐1β, which induces convulsion. The inhibitory cytokines of IL‐10 and IFN‐γ were elevated in the early phase in CSF. Comparing them with other patients, the elevation of the cytokine levels were generally mild. Considering that the prognosis of this MERS case was favorable and high levels of inhibitory cytokines including IL‐10 and IFN‐γ might work to localize the lesion and to prevent sequelae.

Production of chemokines in respiratory syncytial virus infection with central nervous system manifestations

Respiratory syncytial virus (RSV) infection in children can be associated with acute encephalopathy. However, the roles of cytokines in the cerebrospinal fluid (CSF) of such patients remain unevaluated. In this study, a profile of 17 cytokines was determined for eight RSV-infected children with neurological complications. In one patient with high levels of 13 cytokines, a cytokine storm was considered to have occurred. Interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1β levels were also high in other patients. These data suggest that chemokines in CSF play roles in neurological complications in RSV-infected children.

Rapid diagnosis of bacterial meningitis by using multiplex PCR and real time PCR

Abstract Background : The purpose of the present study was to improve a method for a rapid identification of bacteria in bacterial meningitis by using multiplex polymerase chain reaction (PCR).

Therapy of childhood generalized morphea: case reports and reviews of the literature of Japanese cases

Correspondence: Hisashi Kawashima, Department of Paediatrics, Tokyo Medical University, 6 7 1 Nishishinjuku, Shinjuku-ku, Tokyo160 0023, Japan. Email: hisashi@tokyo-med.ac.jp Received 29 March 2004; revised 19 January 2005; accepted 28 February 2005. Generalized morphea (GM) causes not only pathological changes of the skin but also progressive contracture of joints. GM, especially in childhood, is very rare and there is no established therapy. Although steroids and cyclosporine are used in some cases, neither the effects nor the doses have been determined. We experienced two children with GM, and used methotrexate (MTX) and steroids, and both cases responded differently. In order to fi nd an improved therapy for GM in childhood we investigated the courses and compared the literature.

Transaminase in rotavirus gastroenteritis.

Background:  Children infected with rotavirus often show increased levels of transaminase, and symptoms are characterized by white stool, similar to biliary atresia. Rotavirus infections are also sporadically accompanied with convulsions, encephalopathy and Reye syndrome. The aim of the present study was therefore to investigate transaminase and interleukin (IL)‐6 levels in rotavirus infection, in order to better understand their clinical significance.

Extraordinary Changes in Excitatory Amino Acid Levels in Cerebrospinal Fluid of Influenza-Associated Encephalopathy of Children

The correlation between the glutamate–glutamine cycle and nitric oxide (NO) production in the central nervous system (CNS) of a new type of influenza-associated encephalopathy in children is discussed. When measurements of several amino acids and NOx (nitrite/nitrate) levels in the cerebrospinal fluid (CSF) using HPLC-fluorescence and -UV methods, respectively, were made, the CSF glutamate levels of patients with the new type of encephalitis were significantly lower, and both glutamine and NOx levels were significantly higher than those of the control group and the patients of the meningitis group. Results indicate that the turnover rate of glutamate in CNS, particularly in the brain, increases in the influenza-associated encephalopathy. The high mortality in the disease may correlate with the hyperactivity of supra-spinal glutamate neurons and the subsequent high activity levels of NOx in CNS.

mRNA expression of T-helper 1, T-helper 2 cytokines in autoimmune hepatitis in childhood.

Background: In the pathology of autoimmune hepatitis the immunity mechanism of T‐helper 1 (Th1) and Th2 cells was recently evaluated. The purpose of the present study was to measure the mRNA levels in peripheral mononuclear cells and serum cytokines obtained from children with autoimmune hepatitis for a better understanding of the mechanism.