Yoshihiro Matsuzono

Epidemiology of influenza-associated encephalitis-encephalopathy in Hokkaido, the northernmost island of Japan

Abstract Background : It is well known that acute onset brain dysfunction, which usually is diagnosed as encephalitis or encephalopathy, occurs in association with influenza. However, this may have been underestimated as a rather infrequent event. Sixty‐four infants and children developed encephalitis‐encephalopathy during the five recent influenza seasons in Hokkaido, the northernmost island of Japan.

Interleukin-6 in cerebrospinal fluid of patients with central nervous system infections

Interleukin(IL)‐6 levels were measured in cerebrospinal fluid (CSF) and serum samples from pediatric patients with central nervous system (CNS) infections by means of an enzyme‐linked immunosorbent assay. Mean IL‐6 concentrations in CSF samples from patients with bacterial meningitis (49017 44 730 pg/ml) were significantly higher than those in patients with aseptic meningitis (10761572 pg/ml) or encephalitis (409835 pg/ml). In aseptic meningitis and encephalitis, IL‐6 levels in serum were within the lower ranges (< 100 pg/ml), in contrast with the highly elevated levels found in bacterial meningitis (14 33218 385 pg/ml). In 5 of the 15 patients with encephalitis, elevated levels of IL‐6 were observed in the initial CSF samples despite normal findings of routine CSF examinations. Also, sequential CSF samples revealed that there was an increase in the CSF cell count in two of the five patients. These results validated the potential of measuring IL‐6 in CSF samples for the purpose of providing additional information on routine laboratory test results. D Central nervous system infection, cerebrospinal fluid, children, enzyme‐linked immunosorbent assay, interleukin‐6.

Analysis of mycoplasmal pleural effusion by the polymerase chain reaction

Ten pediatric patients with mycoplasmal pleuritis were tested for the presence of Mycoplasma pneumoniae in pleural fluid by the polymerase chain reaction (PCR). Three of the four PCR positive cases left a persistent consolidation. The remaining one was an infant who required mechanical ventilation. PCR may be useful in predicting delayed resolution of roent- genographic abnormality.

Nested amplification protocol for the detection of Mycobacterium tuberculosis

Several methods for rapid diagnosis of tuberculosis have been devised through DNA amplification. However, the chemically strong cell wall of the species, the presumptively low numbers of organisms and their uneven distribution in clinical samples, and the lack of a “gold standard” for diagnosing tuberculosis, have hindered the routine clinical use of this method. In a pediatric patient group, these factors are more perplexing. To circumvent these problems, we made use of nested amplification and developed a standard protocol for extracting DNA from various forms of clinical samples which were suitable to our clinical laboratory. It is our impression that the overall sensitivity, including technical bias accompanying this method, is equal to, or at least greater than, that of culture. Most notably, the rapidity in obtaining results and the simplicity in handling, storage and transfer of samples are the principal advantages of this method.

Measles virus-specific immunoglobulin G subclass response in serum and cerebrospinal fluid

BACKGROUND While many previous studies have focused on the impairment in the cellular immunity during measles virus infection, to date, a limited amount of data is available concerning the virus-specific IgG subclass response during measles virus infection. OBJECTIVE The purpose of this study is to analyze the measles virus infection on the basis of virus-specific IgG subclass (G 1 and G 3). STUDY DESIGN Frozen-stored, serum and/or cerebospinal fluid samples from three groups of patients were tested retrospectively; Group 1 comprised 14 patients with measles primary infection, group 2, ten patients with reinfection/vaccine failure, and group 3, seven patients with subacute sclerosing panencephalitis. The method used was a modified ELISA method utilizing the Enzygnost IgG detection kit with mouse-monoclonal antibodies (clone HP6091 for IgG 1 and clone HP6050 for IgG 3). Avidity testing for each subclass IgG was also performed for selected samples by means of an 8 M urea-denaturation method. RESULTS In group 1, the IgG 3 could be detected in serum within 7 days from the onset of rash more frequently than IgG 1. In the cases of group 2, both subclasses were detected in very acute phase serum samples. In these cases, the IgG 1-specific avidity was always higher than that of IgG 3. In group 3, the subclass IgGs detected in the cerebrospinal fluid had a lower avidity than those in the serum. CONCLUSIONS Our results suggested that in measles virus infection, like other viral infections, the IgG 3 response normally occurs before the IgG 1 response, and plays a major role in the acute phase immunity during the primary infection, while the IgG 1 plays a major role in the maintenance of immunity. Continuously produced IgG 1 and IgG 3 in the central nervous system in cases of subacute sclerosing panencephalitis may be derived from cell populations different from those in the blood.

Measles encephalomyelitis in a patient with a history of vaccination

Secondary vaccine failure (SVF) of measles is generally believed to run a milder course of illness than an ordinary course of infection. Severe complications such as central nervous system involvement have rarely been reported. A 12 year old girl, who had received a live attenuated measles vaccine 10 years earlier, developed an encephalomyelitis in the absence of symptoms indicative of ordinary measles such as Koplik spots. Anti‐measles hemagglutination inhibition (HI) titer and measles IgM and IgG anitbody titers were measured in a commercial laboratory. Measles virus genomic sequence was detected by polymerase chain reaction. Both serum and cerebrospinal fluid (CSF) samples obtained at acute phase already showed extremely high titers of HI (x 8192 in serum and x 1024 in CSF, respectively) and IgG antibody along with the presence of IgM antibody. Polymerase chain reaction detected the measles virus genomic sequence in the acute phase CSF. The patients definite history of measles vaccination, high titers of HI and IgG antibodies observed at the very early stage of illness and the clinical course indicated that this patient had an encephalomyelitis due to SVF of measles. It is suggested that measles virus can be a pathogen of encephalitis without symptoms indicative of ordinary measles in individuals who received live attenuated measles vaccines.

Pulmonary aspergillosis and pseudosequestration of the lung in chronic granulomatous disease

We present a case of chronic granulomatous disease with an angiographically proven pseudo-sequestration of the lung. The patient was a 15-year-old boy who was admitted to the hospital with symptoms of fever, cough, hemoptysis and a subcutaneous abscess.Aspergillus fumigatus was isolated from the sputum and the abscess. During treatment, angiography demonstrated on anomalous blood supply to the right middle lobe. The therapeutic implications of pseudo-sequestration of the lung for the treatment of chronic granulomatous disease are discussed.

Acute encephalitis–encephalopathy during influenza epidemics in Japanese children

Abstract Background: We previously reported an epidemiological aspect of influenza-associated encephalitis/encephalopathy in Japan. Patients: Case 1 is a 7-year-old boy who survived, and case 2 is a 5-year-old boy who died with a fulminant course. Results: Both patients showed remarkably high levels of IL-6 in cerebrospinal fluid and a postmortem examination of case 2 revealed generalized vasculopathy. Conclusion: The generalized impairment of vascular endothelial cells caused by highly activated cytokines must play a central role in the pathophysiology of this disease.