A Combination Therapy for Kawasaki Disease with Severe Complications: a Case Report.

Kawasaki disease (KD) is a form of acute multisystem vasculitis that presents with various complications, including coronary artery aneurysm. Heart failure and brain damage are rare, but life-threatening complications are associated with KD. Here, we describe a 4-year-old girl who developed intravenous immunoglobulin-resistant KD with both left ventricular failure and acute encephalopathy. On day 8 of the illness, the low left ventricular ejection fraction, mitral regurgitation, and low blood pressure, which required continuous administration of dobutamine, were observed during the treatments for KD, including intravenous immunoglobulin. She also appeared unconscious, where the electroencephalogram showed slow waves of activity in all regions of the brain. The cardiac performance improved after she received plasma exchange for three days. However, her unconsciousness with slow waves of activity on electroencephalogram and fever continued after the plasma exchange. Therefore, she was treated with methylprednisolone pulse, followed by prednisolone, as well as intravenous immunoglobulin. Finally, she recovered without any cardiac or neurological sequelae not only at the time she was discharged, but also throughout the follow-up period. The combination therapy using plasma exchange and methylprednisolone pulse may be a treatment option for severe KD with left ventricular failure and acute encephalopathy complications.

Acute Focal Bacterial Nephritis Associated With Central Nervous System Manifestations: A Report of 2 Cases and Review of the Literature.

Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney presenting as an inflammatory mass without frank abscess formation. In children, most patients with AFBN present with nonspecific conditions, such as fever, vomiting, and abdominal pain. A small number of reported cases are accompanied by neurological symptoms, including meningeal irritation, unconsciousness, and seizures. We experienced 2 rare cases of AFBN associated with central nervous system lesions. The first case was a 3-year-old girl who had neurological symptoms, including unconsciousness and seizures, with AFBN associated with acute reversible encephalopathy. The second case was a 5-year-old girl who had neurological symptoms, including unconsciousness, with AFBN accompanied by clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

Severe Acute Subdural Hemorrhages in a Patient with Glutaric Acidemia Type 1 under Recommended Treatment.

Glutaric acidemia type 1 is a rare autosomal recessive disease caused by a deficiency of glutaryl-CoA dehydrogenase. Previous studies have reported subdural hemorrhage in untreated patients with glutaric acidemia type 1. However, there is only one report of severe acute subdural hemorrhage after minor head trauma in a patient with glutaric acidemia type 1 under guideline-recommended treatment. We report a second case of life-threatening severe acute subdural hemorrhage after a minor head trauma in a patient with glutaric acidemia type 1. This patient was previously diagnosed by newborn screening, and treatment began at 25 days of age. Early diagnosis and guideline-recommended treatment produce better outcomes for patients with glutaric acidemia type 1, although the risk of subdural hemorrhage remains.

Affinity for music in Wolf-Hirschhorn syndrome: two case reports.

BACKGROUND: Wolf-Hirschhorn syndrome is a congenital malformation syndrome resulting from deletion of the short arm of chromosome 4. Individuals with Wolf-Hirschhorn syndrome may have a "Greek warrior helmet" appearance, growth retardation, developmental delay, muscular hypotonia, epilepsy, and difficulty with language including verbal communication. An affinity for music has not previously been reported in these patients. PATIENTS: We describe two patients with Wolf-Hirschhorn syndrome who both have a strong affinity for music. One patient is a 20-year-old woman who likes to listen to music all day and can hum many tunes. The other patient is a 9-year-old girl who is calmed by music and received music therapy, with subsequent improvement in her communication skills (eye contact, joint attention, and vocalizations to request music). CONCLUSIONS: Individuals with Wolf-Hirschhorn syndrome may have a strong affinity for music and may benefit from music therapy. Additional studies are needed to investigate the interest in music in individuals with Wolf-Hirschhorn syndrome.

[Clinical efficacy and pharmacokinetics of lamotrigine for childhood-onset intractable epilepsy].

OBJECTIVE: We investigated the clinical efficacy and pharmacokinetics of lamotrigine (LTG) as an add-on therapy in childhood-onset intractable epilepsy. METHODS: We reviewed the charts of 28 outpatients who had received LTG as an add-on therapy. The data collected included epilepsy type, seizure frequency, concomitant anti-epileptic drugs, dosage of LTG and LTG serum levels. Furthermore, we reviewed the relationship between the LTG serum levels (microg/ml) and dosage of LTG (mg/kg/day), as well as the relationship between the LTG serum levels (microg/ml) and clinical efficacy in the following 2 groups:the valproate sodium (VPA) combination group and the non-VPA combination group. RESULTS: A reduction of 50% or more in seizure frequency was observed in 10 patients. In addition, there was a high correlation between the LTG serum levels and the dosage of LTG in each group. In the VPA combination group, the average of LTG serum levels in patients with adequate therapeutic response (50% reduction in seizure frequency) was higher than that in patients without adequate therapeutic response. In the non-VPA combination group, the average LTG serum level in adequate response patients was lower than that in patients without adequate therapeutic response. However, the epilepsy types of adequate response patients differed in the two groups. CONCLUSIONS: The LTG serum level is predictable based on the dosage of LTG. It was judged that the effective blood concentration of LTG differed when used with VPA, although factors other than the combined use of VPA should have been taken into consideration also.

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.

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.

Liver-specific mitochondrial respiratory chain complex I deficiency in fatal influenza encephalopathy.

We report on a 4-year-old boy who died from influenza encephalopathy. The clinical course and microscopic findings of the autopsied liver were compatible with Reye's syndrome. We examined the mitochondrial respiratory chain function by blue native polyacrylamide gel electrophoresis (BN-PAGE), western blotting, and respiratory chain enzyme activity assays. The activity of liver respiratory chain complex (CO) I was markedly decreased (7.2% of the respective control activity); whereas, the other respiratory chain complex activities were substantially normal (CO II, 57.9%; CO III, 122.3%; CO IV, 161.0%). The activities of CO I-IV in fibroblasts were normal (CO I, 82.0%; CO II, 83.1%; CO III, 72.9%; CO IV, 97.3%). The patient was diagnosed with liver-specific complex I deficiency. This inborn disorder may have contributed to the fatal outcome. We propose that relying only on fibroblast respiratory chain complex activities may lead to the misdiagnosis of liver-specific complex I deficiency.

Detection of group a rotavirus RNA and antigens in serum and cerebrospinal fluid from two children with clinically mild encephalopathy with a reversible splenial lesion.

We report on two children with mild encephalopathy with a reversible splenial lesion associated with group A rotavirus (GARV) infection. We examined stool, serum, and cerebrospinal fluid samples to determine the presence of the GARV VP7 gene and GARV antigen by reverse-transcription PCR and enzyme-linked immunosorbent assay, respectively. GARV antigen was detected in stool samples from both patients. The GARV G genotype was G9 in one child and G3 in the other. GARV antigens were also found in both serum samples. However, the GARV VP7 gene was detected in only one serum sample, which was collected on the first day of symptomatic illness. Neither GARV antigen nor the VP7 gene was detected in cerebrospinal fluid samples. Both patients had excellent outcomes. Our results suggest that the reversible splenial changes in our patients might have been caused by indirect effects to the central nervous system subsequent to viral infection.

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.

Rotavirus antigenemia and genomia in children with rotavirus gastroenteritis.

We investigated group A rotavirus (GARV) antigenemia and genomia in children with rotavirus gastroenteritis. A total of 16 patients (2-29 months old), who received a diagnosis of GARV gastroenteritis using a commercial rapid test, were enrolled in this study. The sera from the patients were tested for the presence of GARV antigen and the VP7 and NSP3 genes using an enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction, respectively. Furthermore, when the VP7 gene was amplified, G type was identified and compared with that of GARV from the fecal samples of the patients. GARV antigen was detected in 12 of 16 serum samples (75.0%). No GARV antigen was found in infants that were 6 months old or younger. Thirteen of 16 serum samples (81.3%) were positive for GARV genes. In cases where both antigen and gene analyses were conducted, either GARV antigens or genes, or both, were detected in all cases. The GARV antigen levels of serum collected at 2 days of illness or more were significantly higher than were the levels in the samples obtained from the 1st day. Furthermore, the ELISA optical density values of patients with convulsion were significantly higher than were those of patients without convulsion, suggesting that the antigen level is associated with disease severity.

A case of D-lactic acid encephalopathy associated with use of probiotics.

A five year old girl was admitted to the hospital for evaluation of intermittent ataxia. She had undergone serial resections of the small intestine after birth, resulting in short bowel syndrome. Lactomin was prescribed for watery diarrhea at twice the regular dose 2 weeks before the onset of neurologic symptoms. D-lactic acidosis was diagnosed on the basis of a plasma D-lactate level of 5.537 mmol/l. Lactomin was discontinued, and she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis and should therefore be avoided in patients with short bowel syndrome.

Detection of rotavirus RNA and antigens in serum and cerebrospinal fluid samples from diarrheic children with seizures.

Group A rotavirus (GARV) genes (the VP7 and NSP3 genes) in acute-phase cerebrospinal fluid (CSF), sera and stool samples from 6 children with convulsions accompanied by GARV gastroenteritis were investigated by reverse transcription-polymerase chain reaction (RT-PCR). When the VP7 gene was amplified from the samples, the G genotype (G type) of GARV was determined by RT-PCR. GARV genes were detected in the CSF samples of all 6 children, in 2 of the 3 blood samples, and in all of 4 stool samples. The G typing of GARV from 12 of a total of 13 samples indicated that G3 was the predominant G type in all samples. GARV antigens were detected by enzyme-linked immunosorbent assay in all of the 3 tested sera samples, while no GARV antigens were detected in any of the 5 tested CSF samples. We confirmed the presence of GARV genomes in the CSF samples from all of the children with rotavirus-associated seizures, including encephalopathy. However, the relationship between convulsions and the existence of GARV RNA in CSF remains unclear and further study is required.

Event-related potentials in response to 3-D auditory stimuli.

To evaluate auditory spatial cognitive function, age correlations for event-related potentials (ERPs) in response to auditory stimuli with a Doppler effect were studied in normal children. A sound with a Doppler effect is perceived as a moving audio image. A total of 99 normal subjects (age range, 4-21 years) were tested. In the task-relevant oddball paradigm, P300 and key-press reaction time were elicited using auditory stimuli (1000 Hz fixed and enlarged tones with a Doppler effect). From the age of 4 years, the P300 latency for the enlarged tone with a Doppler effect shortened more rapidly with age than did the P300 latency for tone-pips, and the latencies for the different conditions became similar towards the late teens. The P300 of auditory stimuli with a Doppler effect may be used to evaluate auditory spatial cognitive function in children.

[A case of rhabdomyolysis associated with Salmonella encephalopathy].

We report a case of severe rhabdomyolysis associated with Salmonella encephalopathy. A 3-year-old girl was admitted to our hospital because of status convulsives and unconsciousness. She was diagnosed as having Salmonella encephalopathy with rhabdmyolysis, and was treated by mild hypothermia and mechanical ventilation. Five days later she developed anuria with increased serum levels of myoglobin, CK and creatinine. And the diagnosis of acute renal failure was made. Peritoneal dialysis was begun from 6 days after admission. Hyperinfusion, the usual therapy of rhabdomyolysis, was not performed. She survived showing gradual improvement of renal function and consciousness. In a case of rhabdomyolysis complicating a neurologic disorder, a well-known poor prognostic factor, priority should be given to brain protection rather than to symptomatic treatment of rhabdomyolysis.