Late-onset cerebral arteriopathy in a patient with incontinentia pigmenti.

BACKGROUND: Incontinentia pigmenti (IP) is an X-linked neurocutaneous disorder that can present with cerebral arteriopathy during early infancy. However, no previous reports have demonstrated arteriopathic manifestations during postinfantile childhood in patients with IP. PATIENT DESCRIPTION: We describe a case of IP in a 2-year-old girl who developed encephalopathic manifestations associated with influenza A infection. She presented diffuse magnetic resonance imaging abnormalities involving the cortices, subcortical white matter, corpus callosum, basal ganglia, and thalami, resembling the findings in early infantile cases reported in the previous literatures. Magnetic resonance angiography demonstrated attenuation of the cerebral arteries. Proinflammatory cytokines and chemokines were upregulated in the cerebrospinal fluid. Left hemiplegia remained following the remission of the arteriopathic manifestations. Genetic analyses revealed a novel type of mutation in the IKBKG gene. CONCLUSION: Our findings indicate that patients with IP can develop destructive cerebral arteriopathy even after early infancy. The similarities in magnetic resonance imaging abnormalities between our patient and the previously reported infantile patients may be explained by the underlying immunologic pathophysiology of IP.

Long-term prognosis of epilepsy in patients with cerebral palsy.

AIM: To assess the long-term natural course and prognosis of epilepsy in patients with cerebral palsy (CP). METHOD: We retrospectively collected data for 72 patients (36 males, 36 females) with CP who had epilepsy who visited our institutions between 1980 and 2015. The data from medical records, electroencephalography (EEG), and neuroimaging findings were reviewed. Time-to-event statistical analyses were performed to analyse the remission outcome and the Cox regression model was used for multivariate analyses. RESULTS: Median age at onset of epilepsy was 2 years 0 months, and 17 years 0 months at the latest follow-up. In total, 34 patients (47%, 0.043 per person-year) achieved seizure remission at a median age of 11 years 0 months. Favourable factors for seizure remission included older age, motor disability being able to roll over/crawl but not able to sit, intellectual disability with an IQ between 36 and 70, normal findings on neuroimaging, and CP type other than spastic quadriplegia. In multivariate analysis, spastic quadriplegia was found to be associated with continued seizure activity. Antiepileptic drugs could be discontinued without relapse in 10 patients at a median age of 16 years 6 months, occurring 11 years 6 months after the onset of epilepsy. The drugs were terminated if the patient was aged at least 10 years and had perinatal causative aetiology and normalization or amelioration of epileptiform discharges on EEG. INTERPRETATION: The remission rate of epilepsy in CP increases up to young adulthood, and termination of antiepileptic drugs can be considered in selected cases at older ages. WHAT THIS PAPER ADDS: The remission rate of epilepsy in cerebral palsy increases up to 20 years after onset. In some cases, antiepileptic drugs (AEDs) can be terminated without relapse. Older age, perinatal aetiology, and improvement on electroencephalography are favourable factors for terminating AEDs.

PRONÓSTICO A LARGO PLAZO DE LA EPILEPSIA EN PACIENTES CON PARÁLISIS CEREBRAL: OBJETIVO: Evaluar el curso natural y pronóstico a largo plazo de la epilepsia en niños con parálisis cerebral (PC). MÉTODO: Recopilamos retrospectivamente los datos de 72 pacientes (36 varones, 36 mujeres) con PC que habían tenido epilepsia y concurrieron a nuestras instituciones entre 1980 y 2015. Los datos de los registros médicos, electroencefalográficos (EEG) y los hallazgos de neuroimágenes fueron revisados. Se realizaron análisis estadísticos de tiempo - evento para analizar los resultados de la remisión y se utilizó el modelo de regresión de Cox para los análisis multivariados. RESULTADOS: La edad media del comienzo de la epilepsia fue a los 2 años, y el seguimiento más tardío fue a los 17 años. En total, 34 pacientes (47%, 0,0043 por persona / año) alcanzaron la remisión de las convulsiones a la edad media de los 11 años. Los factores favorables para la remisión de las convulsiones incluyeron mayor edad, la discapacidad motora que sea capaz de rolar, gatear aunque no sentarse, discapacidad intelectual con un CI entre 36 y 70, hallazgos normales en neuroimágenes y otro tipo de PC diferente de la cuadriparesia espástica. En el análisis multivariado, se encontró que la cuadriparesia espástica se asociaba con una actividad convulsiva constante. Las drogas antiepilépticas pudieron ser discontinuadas sin recaídas en 10 pacientes a la edad media de 16 años y 6 meses, 11 años y 6 meses después del comienzo de la epilepsia. Las drogas fueron suspendidas si el paciente tenía por lo menos10 años de edad, etiología perinatal y normalización y disminución de las descargas epilépticas en el EEG. INTERPRETACIÓN: La tasa de remisión de la epilepsia en la PC aumenta hasta la edad adulta temprana, y la terminación de los fármacos antiepilépticos puede considerarse en casos seleccionados a edades más avanzadas.

PROGNÓSTICO EM LONGO PRAZO DA EPILEPSIA EM PACIENTES COM PARALISIA CEREBRAL: OBJETIVO: Avaliar o curso natural em longo prazo e prognóstico da epilepsia em pacientes com paralisia cerebral (PC). MÉTODO: Coletamos retrospectivamente dados coletados para 72 pacientes (36 do sexo masculino, 36 do sexo feminino) com PC que tinham epilepsia e visitaram nossas instituições entre 1980 e 2015. Os dados dos prontuários médicos, eletroencefalografia (EEG), e achados de neuroimagem foram revisados. Análises estatísticas de tempo para o evento foram realizadas para o resultado de remissão e o modelo de regressão de Cox foi usado para análise multivariada. RESULTADOS: A idade mediana do início da epilepsia foi 2 anos e 0 meses, e 17 anos e 0 meses no último acompanhamento. No total, 34 pacientes (47%, 0,043 por pessoa-ano) apresentaram remissão das convulsões em uma idade mediana de 11 anos 0 meses. Fatores favoráveis para a remissão incluíram maior idade, deficiência motora sendo capaz de rolar/arrastar, mas não de sentar, deficiência intelectual com entre 36 e 70, achados normais de neuroimagem, e outros tipos de PC que não quadriplegia espástica. Na análise multivariada, a quadriplegia espástica foi associada com atividade convulsiva continuada. Drogas antiepilépticas puderam ser descontinuadas sem recidiva em 10 pacientes, em uma idade mediana de 16 anos e 6 meses, ocorrendo 11 anos e 6 meses após o início da epilepsia. Os medicamentos foram cessados se o paciente tinha ao menos 10 anos de idade e teve etiologia causadora perinatal e normalização ou melhora das descargas epileptiformes ao EEG. INTERPRETAÇÃO: A taxa de remissão da epilepsia em PC aumenta até a idade adulta jovem, e a cessação das drogas antiepilépticas pode ser considerada em casos selecionados de maior idade.

Use of high b value diffusion-weighted magnetic resonance imaging in acute encephalopathy/encephalitis during childhood.

AIM: To determine the use of high b value diffusion-weighted imaging (DWI) in the diagnosis and assessment of acute febrile encephalopathy/encephalitis in childhood. SUBJECTS AND METHODS: We enrolled 22 children, for whom we examined DWI with b=1000s/mm2, DWI with b=3000s/mm2, and apparent diffusion coefficient (ADC) map with b=1000 during the acute phase of febrile encephalopathy/encephalitis. Clinical diagnoses included acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n=6), clinically mild encephalopathy/encephalitis with a reversible splenial lesion (MERS; n=6), and herpes simplex virus encephalitis (HSE; n=3), unclassified acute encephalopathy/acute encephalitis (n=2); acute encephalitis with refractory, repetitive partial seizures (AERRPS; n=1); other encephalopathy (n=1); infarction (n=1); head injury (n=1); or mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (n=1). The diagnostic quality of brain lesions was compared between b=1000 and b=3000 DWI images by visual inspection. In addition, we attempted a quantitative assessment using apparent diffusion coefficient (ADC) value and an index of signal intensity (SI) ratio, defined as the mean SI at the affected lesion divided by the mean SI at the pons. RESULTS: High intensity lesions were either visible only on b=3000 DWI (n=5; 2 AESD, 1 MERS, 1 HSE, and 1 unclassifiable encephalopathy) or more effectively identified on b=3000 DWI than on b=1000 DWI (n=17). The outcome of the former five subjects was favorable, without motor or intellectual sequelae. The mean SI ratio of b=3000 was significantly greater than that of b=1000 in AESD and MERS subgroups as well as in all 22 subjects. Mean ADC values were lower in the AESD and MERS than that in the HSE subgroups. CONCLUSION: We concluded that b=3000 DWI was superior to b=1000 DWI in detecting abnormal lesions in acute encephalopathy/encephalitis during childhood.

[Effect of food thickener on disintegration and dissolution of magnesium oxide tablets].

It has been reported that magnesium oxide tablets are excreted in a non-disintegrated state in the stool of patients when the tablets are administered after being immersed in a food thickener. Therefore we examined whether immersion in a food thickener affects the pharmacological effect in patients taking magnesium oxide tablets, and whether immersion affects its disintegration and solubility. The mean dosage (1705 mg/d) was higher for patients who took tablets after immersion in a food thickener than for those who took non-immersed tablets (1380 mg/d). The disintegration time and dissolution rate of the immersed tablets were lower than those of non-immersed tablets in vitro. Furthermore, components that constitute the food thickener and differences in composition concentrations differentially affect the disintegration and solubility of magnesium oxide tablets. This suggests that commercially available food thickeners are likely to be associated with changes in the degradation of magnesium oxide tablets, and they therefore should be carefully used in certain clinical situations.

Molecular mechanisms of hereditary persistence of alpha-fetoprotein (AFP) in two Japanese families A hepatocyte nuclear factor-1 site mutation leads to induction of the AFP gene expression in adult livers.

alpha-Fetoprotein (AFP) is produced abundantly in fetal liver but is hardly detectable in adults. In this study, we investigated two unrelated Japanese families with hereditary persistence of AFP. A g-->a substitution at nucleotide -119 (-119g-->a) in the hepatocyte nuclear factor (HNF)-1 binding site of the AFP promoter was identified in both families. The activity of the wild- or variant-type human AFP promoter was evaluated by in vitro and in vivo transfection experiments. This substitution in the AFP promoter significantly stimulated its transcriptional activity in human hepatoma cells, regardless of their prior AFP production. The variant-type AFP promoter was also active in adult mouse livers in vivo. Additionally, overexpression of HNF-1alpha stimulated the activity of both the wild- and variant-type AFP promoters in hepatoma cells. HNF-1alpha expression also activated both AFP promoters even in nonhepatoma cells, and this activation was suppressed by nuclear factor (NF)-I overexpression. These results indicate that an HNF-1 binding site mutation leads to induction of the AFP gene expression in adult liver, and suggest that competition between HNF-1 and NF-I in this region is involved in transcriptional regulation of the AFP gene during hepatic development.

Pharmacokinetic study of recombinant human hepatocyte growth factor administered in a bolus intravenously or via portal vein.

Hepatocyte growth factor (HGF) stimulates liver regeneration and has the potential to be a therapeutic agent for fatal liver diseases, including fulminant hepatic failure and liver cirrhosis. In this study, we investigated the pharmacokinetics of recombinant human HGF, which will be soon available for clinical applications. When recombinant human HGF (0.1mg/kg) was administered intravenously to normal rats, serum levels of human HGF increased to 89.7+/-20.6ng/ml 5min after the bolus injection, followed by a decrease with a half-life of 2.4min. Recombinant HGF administered intravenously was distributed primarily to the liver and induced c-Met tyrosine phosphorylation in liver tissues. In comparison, rats given recombinant human HGF via the portal vein exhibited lower serum HGF and an increase in hepatic distribution. Additionally, when compared with normal rats, those with 70% partial hepatectomy or liver cirrhosis showed an increase in serum levels of human HGF with a prolonged half-life. These results suggest that, despite a short half-life, bolus injection of recombinant human HGF may induce therapeutic effect in patients with fatal live disease, and that the dose of this recombinant protein should be modulated according to the degree of liver injury.

Sesquiterpenoids from Artemisia gilvescens and an anti-MRSA compound.

A new secoguaianolide sesquiterpene (1) was isolated along with its three stereoisomers (2-4) from the nonmedicinal plant Artemisia gilvescens. The structure of 1 was elucidated to be (4S,5S)-dihydro-5-[(1R,2S)-2-hydroxy-2-methyl-5-oxo-3-cyclopenten-1-yl]-3-methylene-4-(3-oxobutyl)-2(3H)-furanone on the basis of 2D NMR and other spectroscopic evidence. Five known sesquiterpenoids were also isolated from this plant, and one of them (5) showed activity against methicillin-resistant Staphylococcus aureus (MRSA).