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J Infect Chemother ; 2021 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-33583741


INTRODUCTION: To clarify the pathology of children with acute encephalopathy and other neurological disorders, the involvement of high-mobility group box 1 (HMGB1), which is a representative of danger-associated molecular patterns, and angiogenesis-related growth factors were investigated. PATIENTS AND METHODS: Participants were 12 children with acute encephalopathy (influenza, rotavirus, and others), 7 with bacterial meningitis, and 6 with epilepsy disease (West syndrome). Twenty-four patients with non-central nervous system (CNS) infections as a control group were admitted to our hospital. We examined the levels of HMGB1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and other cytokines in the serum and cerebrospinal fluid (CSF) of the subjects. RESULTS: Serum and CSF HMGB1 levels were significantly higher in the encephalopathy and meningitis groups than in the West syndrome and control groups. CSF HMGB1 levels correlated with those of interleukin-6 and -8. CSF HMGB1 and VEGF levels were correlated, and PDGF showed a positive relationship. CONCLUSION: HMGB1 and angiogenesis-related growth factors appear to play pivotal roles in the pathophysiology of CNS infections.

J Neuroimmunol ; 352: 577475, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33454554


In this study, we assessed circulating immune cells and plasma cytokine levels in 15 pediatric patients with drug-resistant epilepsy (DRE). DRE patients had a significantly higher percentage of CD14+ monocytes positive for IL-1ß, IL-1 receptor antagonist, IL-6, and TNF-α than controls. Significantly higher intracellular levels of IFN-γ in CD4+ T cells and NK cells were also found in DRE patients. The level of IL-1ß+ CD14+ monocytes correlated with seizure frequency, and intracellular levels of IFN-γ in NKT-like cells were negatively correlated with the duration of epilepsy. Peripheral immune cells might be involved in the pathogenesis of DRE.

Am J Med Genet A ; 2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33251766


Several patients with beta-propeller protein-associated neurodegeneration (BPAN)/static encephalopathy with neurodegeneration in adulthood have been reported to present Rett syndrome (RTT)-like features. This report presents an individual with BPAN showing clinical features of RTT. Psychomotor delay and epilepsy onset were noted at 1 year, and regression began at 4 years. Screening of the methyl-CpG binding protein 2 (MECP2) did not show variants. At 22 years, basal ganglia iron deposits were found on magnetic resonance imaging (MRI), and the WD-domain repeat 45 gene (WDR45) variant was identified. Review of the literature showed that BPAN with RTT-like features is associated with more epileptic seizures and less deceleration of head growth, breathing irregularities, and cold extremities than classic RTT with MECP2 variants. These clinical presentations may provide clues for differentiating between these two disorders. However, both WDR45 and MECP2 should be screened in patients presenting a clinical picture of RTT without specific MRI findings of BPAN.

Brain Dev ; 42(7): 523-528, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32336482


BACKGROUND: Riboflavin may prevent migraine episodes; however, there is limited evidence of its effectiveness in pediatric populations. This study investigated the effectiveness of riboflavin and clinical predictors of response in children with migraines. METHODS: We retrospectively reviewed data from 68 Japanese children with migraines, of whom 52 also exhibited another type of headache. Patients received 10 or 40 mg/day of riboflavin. We evaluated the average migraine frequency per month as a baseline and after 3 months of riboflavin therapy to determine the effectiveness and clinical predictors of response. RESULTS: The frequency of migraine episodes was significantly lower at 3 months than at baseline (median, [interquartile range], 5.2 (3-7) vs. 4.0 (2-5); p < 0.01). Twenty-five patients (36.7%) showed 50% or greater reduction in episode frequency (responders), while 18 (26.5%) showed a 25%-50% reduction. We compared responders (n = 25) and non-responders (n = 43) and found no significant differences in sex, familial history, riboflavin dose, migraine type (i.e., presence or absence of aura), age at headache onset, or age at consultation. However, non-responders were more likely to have co-morbid non-migraine headaches (odds ratio, 4.11; 95% confidence interval [CI], 1.27-13.33; p = 0.02); this variable was also significant in a multivariate analysis (adjusted odds ratio, 3.8; 95% CI, 1.16-12.6; p = 0.03). Of the co-morbid headache types, only tension headaches were significant (odds ratio, 0.176; 95% CI, 0.04-0.73; p = 0.013). No adverse effects of riboflavin were identified. CONCLUSIONS: Low-dose riboflavin is safe and modestly effective for migraines in children. It may be especially beneficial for children without other co-morbid headache types.

J Child Neurol ; 35(3): 208-214, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31709864


OBJECTIVE: The present study aimed to determine whether granzymes are implicated in the pathogenesis of infection-associated acute encephalopathy (AE). METHODS: We investigated granzyme and cytokine levels in the cerebrospinal fluid of patients with acute encephalopathy or complex febrile seizures (cFS). A total of 24 acute encephalopathy patients and 22 complex febrile seizures patients were included in the present study. Levels of granzymes A and B were measured using enzyme-linked immunosorbent assay, and levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin 1ß (IL-1ß), IL-1 receptor antagonist (IL-1RA), IL-4, IL-6, IL-8, and IL-10 were assessed using the Bio-Plex suspension array system. RESULTS: Cerebrospinal fluid levels of granzyme A were significantly higher, and those of TNF-α and IL-1RA were significantly lower in the AE group than in the cFS group; however, no significant differences in the levels of granzyme B, IFN-γ, IL-1ß, IL-4, IL-6, IL-8, and IL-10 were observed between the 2 groups. In addition, no significant differences in granzyme A, granzyme B, or cytokine levels were observed between acute encephalopathy patients with and those without neurologic sequelae. CONCLUSIONS: Our findings indicate the involvement of granzyme A in the pathogenesis of acute encephalopathy.