Shinya Koizumi

IL-8 in Cerebrospinal Fluid from Children with Acute Encephalopathy is Higher than in that from Children with Febrile Seizure

We identify possible differences in the cytokine/chemokine profiles in cerebrospinal fluid (CSF) from children with encephalopathy and febrile seizure. Interleukin (IL)‐1β, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, interferon‐γ, tumour necrosis factor‐α, granulocyte colony‐stimulating factor, granulocyte monocyte colony‐stimulating factor, monocyte chemoattractant protein‐1 and macrophage inflammatory protein‐1β were measured simultaneously in CSF supernatants from children with encephalopathy (n = 8), febrile seizure (n = 16) and fever without neurological complications (n = 8). IL‐8 in CSF from children with encephalopathy was significantly elevated compared to that in CSF from children with febrile seizure and fever without neurological complications. IL‐8 in CSF was also higher than serum IL‐8, suggesting that increased IL‐8 was generated from glia cells or astrocytes, not by leakage from serum. Increased IL‐8 in CSF in encephalopathy may protect against severe brain damage.

IL-17 is elevated in cerebrospinal fluids in bacterial meningitis in children.

Bacterial meningitis has a poor prognosis and neurologic complications. The present study aimed to investigate the cytokine/chemokine network in cerebrospinal fluid (CSF) from children with bacterial meningitis and aseptic meningitis. Interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta, were measured simultaneously in CSF supernatants. We found that, IL-17 was significantly elevated in CSF with bacterial meningitis. We believe that IL-17 plays a key role in neutrophil infiltration into CSF and neuronal protection in bacterial meningitis.

High mobility group box 1 in cerebrospinal fluid from several neurological diseases at early time points.

ABSTRACT The present study aimed to elucidate the possible role of High Mobility Group Box 1 (HMGB1), which is a candidate prognostic marker in diseases that combine inflammation and tissue injury, in acute encephalopathy. HMGB1 in cerebrospinal fluid (CSF) obtained on admission from eight children with acute encephalopathy, and 16 children with febrile seizure, eight children with bacterial/aseptic meningitis, and eight children with fever without neurological symptoms were analyzed using enzyme-linked immunosorbent assay (ELISA). We found no increase in HMGB1 in CSF from acute encephalopathy or in CSF from febrile seizure or fever without neurological complications at early time points, while marked elevation of HMGB1 was seen in CSF from bacterial and aseptic meningitis. In conclusion, HMGB1 is a poor disease marker for acute encephalopathy.

Identification of a novel biomarker candidate, a 4.8-kDa peptide fragment from a neurosecretory protein VGF precursor, by proteomic analysis of cerebrospinal fluid from children with acute encephalopathy using SELDI-TOF-MS

BackgroundAcute encephalopathy includes rapid deterioration and has a poor prognosis. Early intervention is essential to prevent progression of the disease and subsequent neurologic complications. However, in the acute period, true encephalopathy cannot easily be differentiated from febrile seizures, especially febrile seizures of the complex type. Thus, an early diagnostic marker has been sought in order to enable early intervention. The purpose of this study was to identify a novel marker candidate protein differentially expressed in the cerebrospinal fluid (CSF) of children with encephalopathy using proteomic analysis.MethodsFor detection of biomarkers, CSF samples were obtained from 13 children with acute encephalopathy and 42 children with febrile seizure. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology, which is currently applied in many fields of biological and medical sciences. Diagnosis was made by at least two pediatric neurologists based on the clinical findings and routine examinations. All specimens were collected for diagnostic tests and the remaining portion of the specimens were used for the SELDI-TOF MS investigations.ResultsIn experiment 1, CSF from patients with febrile seizures (n = 28), patients with encephalopathy (n = 8) (including influenza encephalopathy (n = 3), encephalopathy due to rotavirus (n = 1), human herpes virus 6 (n = 1)) were used for the SELDI analysis. In experiment 2, SELDI analysis was performed on CSF from a second set of febrile seizure patients (n = 14) and encephalopathy patients (n = 5). We found that the peak with an m/z of 4810 contributed the most to the separation of the two groups. After purification and identification of the 4.8-kDa protein, a 4.8-kDa proteolytic peptide fragment from the neurosecretory protein VGF precursor (VGF4.8) was identified as a novel biomarker for encephalopathy.ConclusionsExpression of VGF4.8 has been reported to be decreased in pathologically degenerative changes such as Alzheimers disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and encephalopathy. Thus, the VGF4.8 peptide might be a novel marker for degenerative brain conditions.

An 8-year-old boy with vertebral artery dissection with cerebellar ataxia featuring suspected vertebral artery hypoplasia

We report an 8-year-old boy with left vertebral artery dissection featuring cerebellar ataxia in which congenital vertebral artery hypoplasia was suspected as a predisposing factor in the dissection. The patient suddenly suffered from vertigo and vomiting while swimming, and he was brought to our department. The initial brain Computed Tomography (CT) demonstrated no abnormalities, and his symptoms disappeared the next morning. However, one month after onset, brain Magnetic Resonance Imaging (MRI) revealed ischemic changes (infarction) in the left cerebellum. Transfemoral angiography showed complete occlusion at the C2 portion of the left vertebral artery, suggesting dissection and diffuse narrowing of the proximal segment of the occlusion site. Three-dimensional CT angiography also revealed diffuse narrowing of the left vertebral artery from the bifurcation of the subclavian artery. He has since been living daily life without any difficulties. The detailed etiology of cerebral artery dissection remains unknown, but arterial anomalies should be considered as a predisposing factor.

Enhanced expression of cytokines/chemokines in cerebrospinal fluids in mumps meningitis in children

Background:  The mumps virus is frequently the causative agent in aseptic meningitis and mumps has still prevailed in Japan. We compared data obtained from patients with mumps meningitis and patients with aseptic meningitis caused by other viruses in order to identify mumps meningitis‐specific cytokine/chemokine alterations in cerebrospinal fluide (CSF).

Theophylline-induced changes in mouse electroencephalograms.

Theophylline can induce life-threatening seizures in humans, especially in infants, but the mechanism of induction remains unknown. We investigated the effects of orally administered theophylline on mouse electroencephalograms (EEGs). ddY mice, which are generally completely free of seizures, were used for the experiments. While EEGs, used as controls, showed no paroxysmal spike discharges, theophylline induced clear spike discharges. This study demonstrated that theophylline administered at doses that achieve low serum concentrations can cause spike discharges in mouse EEGs even without causing clinical seizures, indicating that theophylline plays a potent role in subclinical epileptogenicity.

High prevalence of antibodies against Bartonella henselae with cervical lymphadenopathy in children

Background:  Cat‐scratch disease is the most common form of Bartonella henselae infection. Although reports have shown that CSD is relatively common, they have not shown the prevalence of seropositivity for Bartonella henselae in cases of cervical lymphadenitis and Kawasaki disease, which are relatively common diseases in children.

Cat scratch disease confirmed by immunological and polymerase-chain-reaction-based diagnosis using serum

Cat scratch disease (CSD), which is the most common form of Bartonella henselae infection, is characterized by fever and regional lymphadenopathy following a cat scratch. Although serological examination is the most common method to confirm B. henselae infections, some patients exhibit borderline values of B.-henselae-specific antibody titers and there are many serologically positive patients among healthy children without apparent symptoms of CSD. In addition, it takes at least two weeks to obtain the results of serological diagnosis by the commercially available examination system in Japan, as measurement of the antibody titer is carried out in the USA. On the other hand, nested polymerase chain reaction (PCR) has been developed to detect the DNA of pathogens and has been applied for rapid diagnosis of CSD. Here, we report familial cases of CSD confirmed by indirect immunofluorescence assay and nested PCR methods.

The Incidence of Pediatric Invasive Bacterial Diseases in Nippon Medical School Chiba Hokusoh Hospital before and after the Introduction of Conjugate Vaccines

The introduction of the Haemophilus influenzae type b (Hib) vaccine and the 7-valent pneumococcal conjugate vaccine (PCV7) has led to dramatic reductions in cases of invasive H. influenzae disease and invasive pneumococcal disease (IPD). After the introduction of the PCV7 and the 13-valent pneumococcal conjugate vaccine (PCV13), the number of children with IPD markedly decreased in our hospital. However, since 2015, three children with IPD have been admitted to our hospital. We analyzed the serotype, multilocus sequence type, and antimicrobial susceptibility of Streptococcus pneumoniae strains isolated in these newly diagnosed cases. The strains were serotypes 7F and 12F. In addition, we analyzed the incidence of invasive bacterial disease before and after the introduction of conjugate vaccines and found no change in the incidences. We found that cases of IPD and invasive H. influenzae disease clearly decreased following the introduction of the PCV7, the PCV13, and the Hib vaccine, as well as disease caused by antibiotic-resistant strains.