Wakako Ishii

Acute encephalopathy with pandemic (H1N1) 2009 virus infection.

Objectives In April 2009, a novel influenza A (H1N1) pdm virus was identified in Mexico and spread quickly around the world. However, the clinical features of acute encephalopathy associated with 2009 pandemic influenza have not yet been elucidated. Methods We treated 8 patients (3 boys and 5 girls) aged 4 to 11 years (average age, 8 y 3 months) with influenza virus–associated encephalopathy, who presented at our 2 hospitals between July 2009 and March 2010. We investigated the clinical characteristics, treatments, and outcomes in the patients. Results In all patients, brain computed tomography showed mild to severe diffuse cerebral edema, and electroencephalography revealed diffuse high-voltage slow waves. They were all treated with oseltamivir and methylprednisolone pulse therapy. Six patients recovered without any sequelae; however, the remaining 2 had residual neurological sequelae. These 2 patients presented with severe disturbance of consciousness, and their central nervous system symptoms appeared within 12 hours after the onset of fever. One patient had periventricular leukomalacia and symptomatic epilepsy by perinatal brain hypoxia, and the other patient had 1 complex febrile and 2 febrile seizures. Conclusions This study showed that patients with influenza-associated encephalopathy caused by influenza A (H1N1) pdm infection were all older than those with seasonal influenza. Underlying neurological disease or history may be associated with poor prognosis.

A 3-year-old boy with Guillain–Barré syndrome and encephalitis associated with Mycoplasma pneumoniae infection

Mycoplasma pneumoniae is a common cause of respiratory tract illness in children. Among the most common extrapulmonary manifestations are disorders of the central nervous system, including meningitis, meningoencephalitis, cerebellitis, polyneuropathy, acute disseminated encephalomyelitis, and Guillain-Barré syndrome. Guillain-Barré syndrome, also known as acute inflammatory demyelinating polyradiculoneuropathy, is an acute-onset, immune-mediated disorder of the peripheral nervous system. The central nervous system is usually intact in patients with Guillain-Barré syndrome. However, there have been some reports of an association of Guillain-Barré syndrome with central nervous system involvement in children. We report a 3-year-old boy with M. pneumoniae infection associated with Guillain-Barré syndrome and encephalitis. Both serum anti-GM1 ganglioside (IgG and IgM) and anti-galactocerebroside IgG antibodies were detected in our patient: the former in the earlier stage of the disease, and the latter in the later stage. We speculate that anti-GM1 ganglioside was associated more with encephalitis, and anti-galactocerebroside antibody was associated more with GBS in our case. Our patient is the youngest report of Guillain-Barré syndrome with central nervous system involvement, and the first report of a pediatric patient with associated M. pneumoniae infection. Such cases are rarely reported, but highlight the need for awareness of the association of the infection with Guillain-Barré syndrome with central nervous system involvement.

Treatment responses for disseminated intravascular coagulation in 25 children treated with recombinant thrombomodulin: A single institution experience

INTRODUCTION Recombinant thrombomodulin (rTM), which degrades factors Va and VIIIa by activating protein C, has been developed as a new drug for treating disseminated intravascular coagulation (DIC). MATERIALS AND METHODS Since July 2009, we have treated 25 children with DIC using rTM (380 U/kg/day, or 130 U/kg/day for newborns) as a first-line therapy. Median duration of rTM administration was 5 consecutive days (range, 2-13 days). We employed DIC criteria of the Japan Welfare and Health Ministry. The first day on which rTM treatment was given was defined as day 1. RESULTS Median patients age was 3 years. Underlying diseases were hematological disorders (n=13) and severe infection (n=12). Overall, 20 of the 25 patients had recovered from DIC by day 7 and 22 of the 25 patients remained alive at day 28. Median Pediatric Logistic Organ Dysfunction score improved from 11 on day 1 to 2 on day 7 (p=0.009). Laboratory data (median) on day 7 (prothrombin time (PT) ratio, 1.15; fibrin and fibrinogen degradation products (FDP), 9.6 mg/l; D-dimer, 1.6 mg/l FEU; antithrombin, 112%; protein C, 105%) were significantly improved compared to results on day 1 (PT ratio, 1.39; FDP, 21.6 mg/l; D-dimer, 6.4 mg/l FEU; antithrombin, 86%; protein C, 54%). Whereas, 5 patients failed to respond and serious bleeding events were observed in 2 newborns. CONCLUSION The efficacy of rTM cannot be assessed from the present dataset, due to several limitations such as the small heterogenous patient cohort, and the lack of age- and disease-matched controls. Nevertheless, this case-series remains important in terms of enabling further prospective control studies to evaluate the efficacy of rTM in children.

Multiplex PCR for the Detection of 10 Viruses Causing Encephalitis/Encephalopathy and its Application to Clinical Samples Collected from Japanese Children with Suspected Viral.

BACKGROUND Acute encephalitis is a serious neurological condition having a high mortality rate and affecting both children and adults. This study aimed to develop a multiplex PCR method for the simultaneous screening of clinical samples for the presence of the 10 viruses presently considered as the major viral causes of acute encephalitis/ encephalopathy in Asia. METHODS Using previously published primers that have been widely used to screen for herpes virus-6, influenza A virus, human parechovirus, herpes simplex viruses 1 and 2, Japanese encephalitis virus, group A rotavirus, enterovirus, adenovirus, and dengue virus in clinical samples, a single-tube multiplex PCR assay was developed and was tested for its sensitivity and specificity. The method was then applied to screen 57 clinical samples, consisting of 13 fecal samples, 5 throat swabs, 3 post-nasal swabs, 18 serum samples, and 18 cerebrospinal fluid (CSF) samples, collected from 18 hospitalized Japanese children with suspected viral encephalitis/encephalopathy for the target viruses, and the results were compared with those of a monoplex PCR method. RESULTS Positive viral controls of the 10 viruses were correctly typed using this multiplex PCR method. The multiplex PCR method showed high specificity with no unspecific amplification to non-target viruses. The results of applying this PCR method for screening clinical samples showed that 6 fecal samples, 2 serum samples, and 1 CSF sample collected from 7 patients were positive for a virus, specifically group A rotavirus (4 patients, 22.2%), enterovirus (2 patients, 11.1%), or adenovirus (1 patient, 5.6%). In comparison with monoplex PCR, for group A rotavirus, enterovirus, and adenovirus, the sensitivity of this multiplex PCR method decreased for serum, cerebrospinal fluid, and throat swab samples. CONCLUSIONS This newly developed multiplex PCR method is a simple, rapid diagnostic tool and can be used to screen clinical samples for viruses causing acute encephalitis/encephalopathy in children in Asian countries.

Improvement of intractable childhood epilepsy following acute viral infection

In this study, we report 11 patients with intractable childhood epilepsy that improved following acute viral infection. The patients were 8 boys and 3 girls. Six of the 11 children were diagnosed as West syndrome (5 of the symptomatic type and 1 of the cryptogenic type). The remaining 5 children were myoclonic seizures. The patients became seizure free within 6 days following acute viral infections without an exchange or addition of antiepileptic drugs (AEDs). The types of acute viral infections were Exanthema subitum (Roseola infantum) in 5 patients, Rotavirus gastroenteritis in 2 patients, Measles infection in 2 patients, Herpetic stomatitis in 1 patient and Common cold in the remaining patient. Salaam seizures and/or tonic spasms disappeared within 6 days after the onset of viral infections, and hypsarrhythmia evolved to localized spikes on electroencephalography (EEG) in the patients with West syndrome. Epileptic seizures disappeared rapidly and EEG gradually normalized or improved in patients with myoclonic seizures. Four patients became seizure free for 5 years to 20 years. In 6 patients, seizures relapsed within 14 days to 1 month after the disappearance of seizures. One child remained seizure free for 12 months after viral infection. Common factors in 4 children who were continuously seizure free include (1) normal or almost normal findings of brain CT/MRI, (2) normal development prior to the onset of epileptic seizures, and (3) a short time interval between the onset of seizures and the acute viral infection. We propose several hypotheses including an immunological effect for the improvement of intractable childhood epilepsy following acute viral infection. Further study may provide important information concerning the mechanism of seizure control and the applicable to treatment for intractable childhood epilepsy.