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1.
Brain Dev ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39242349

RESUMEN

BACKGROUND: Quantitative EEG is frequently used to monitor children affected by acute encephalopathy (AE), with the expectation of providing comprehensive insights into continuous EEG monitoring. However, the potential of quantitative EEG for estimating outcomes in this context remains unclear. We sought reliable prognostic markers within the color density spectral array (CDSA) of the continuous EEG for AE-affected children undergoing therapeutic hypothermia (TH). METHODS: This retrospective study analyzed CDSA data from eight scalp electrodes of 15 AE-affected children undergoing TH. Two CDSA features were investigated-high-frequency lines (HFLs) and periodic elevation in the low frequency band (PLFB)-along with the corresponding EEG characteristics. The inter-rater reliability for CDSA was assessed by four pediatric neurologists. Outcomes were grouped into either no/mild or severe decline in motor and cognitive functions, then compared with CDSA features. RESULTS: The median EEG recording time was 114 (81-151) h per child. While at least 41 % of HFLs corresponded to typical sleep spindles, 94 % of PLFB aligned with cyclic changes in the amplitude of delta/theta waves on the raw EEG. Inter-rater reliability was higher for HFLs than for PLFB (kappa values: 0.69 vs. 0.46). HFLs were significantly more prevalent in children with no/mild decline than in children with severe decline (p = 0.017), whereas PLFB did not differ significantly (p = 0.33). CONCLUSIONS: This study provides preliminary evidence that reduced HFLs on CDSA predict unfavorable outcomes in AE-affected children undergoing TH. This suggests that maintaining high-frequency waves is critical for optimal brain function.

2.
Pediatr Neurol ; 155: 126-132, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38636169

RESUMEN

BACKGROUND: Various factors contribute to the development of infection-related acute encephalopathy (AE) in children, such as infectious agents and chronic underlying disorders. We studied underlying disorders in children with AE to identify predisposing factors of AE. METHODS: We investigated underlying disorders or past histories in patients with two types of AE from the database in the Tokai area of Japan between 2009 and 2022: 204 patients with AE with reduced subcortical diffusion (AED) and 137 with clinically mild encephalopathy with a reversible splenial lesion (MERS). We compared them with 89 patients with acute disseminated encephalomyelitis (ADEM) to clarify the specific disorders in the two AE types. RESULTS: The prevalence of underlying disorders in AED (34%, 70 patients) was significantly higher than that in ADEM (12%, 11 patients) (P < 0.01). The prevalence of underlying disorders in MERS was 23% (32 patients). The underlying disorders included seizure disorders, premature birth, genetic/congenital disorders, and endocrine/renal diseases. In patients with seizure disorders in AED, five patients (18%) had Dravet syndrome and four (15%) had West syndrome, whereas none with MERS had these syndromes. Twenty-five (12%) of 204 patients with AED, three (2%) with MERS, and one (1%) with ADEM were preterm or low birth weight. CONCLUSIONS: The high prevalence of seizure disorders suggests that seizure susceptibility is an important predisposing factor in AED. Premature birth also has an impact on the development of AED. Caution is required regarding the development of AE in patients with chronic seizure disorders or premature birth.


Asunto(s)
Encefalopatías , Humanos , Masculino , Femenino , Preescolar , Lactante , Niño , Encefalopatías/epidemiología , Encefalopatías/etiología , Encefalopatías/complicaciones , Adolescente , Japón/epidemiología , Prevalencia , Recién Nacido , Encefalomielitis Aguda Diseminada/epidemiología , Encefalomielitis Aguda Diseminada/etiología , Encefalomielitis Aguda Diseminada/complicaciones
3.
Arch Gynecol Obstet ; 309(5): 1909-1918, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37178219

RESUMEN

PURPOSE: Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age. METHODS: A total of 58 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer). RESULTS: The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates. CONCLUSIONS: Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age.


Asunto(s)
Lesiones Encefálicas , Corioamnionitis , Lactante , Femenino , Embarazo , Recién Nacido , Humanos , Recien Nacido Prematuro , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neuroanatomía , Imagen por Resonancia Magnética/métodos , Lesiones Encefálicas/patología
5.
Pediatr Neurol ; 144: 1-4, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37087914

RESUMEN

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder that often manifests after infections or vaccinations. We report two patients who developed MOGAD out of eight patients with juvenile myelomonocytic leukemia (JMML) that has never been reported. METHODS: We investigated two patients with JMML who developed MOGAD among 127 patients with leukemia from 2012 to 2021. RESULTS: Patient 1 was treated for JMML and developed fever and impaired consciousness at two years and one month of age. Magnetic resonance imaging revealed high-intensity lesions in the left frontal and left occipital white matter. The serum anti-MOG antibody test was positive, while the test was negative in the stored serum 45 days before the onset of encephalopathy. He had relapse of MOGAD after steroid therapy and plasmapheresis. Patient 2, who was treated for JMML, became apathetic and mute at three years and seven months of age. Magnetic resonance imaging revealed left frontoparietal subcortical high-intensity lesions. Anti-MOG antibody at the onset of encephalopathy was positive, while it was negative in stored serum 57 days before and 47 days after the onset. CONCLUSION: We treated two patients who developed MOGAD out of eight patients with JMML and none with MOGAD out of 119 patients with acute lymphocytic leukemia, acute myelocytic leukemia, or chronic myelocytic leukemia. The activated autoimmune process via the RAS pathway abnormality may have led to the formation of the anti-MOG antibody and the onset of MOGAD. MOGAD can occur in children with JMML, and abnormalities of the RAS pathway possibly contribute to its onset.


Asunto(s)
Enfermedades Autoinmunes , Encefalopatías , Leucemia Mielomonocítica Juvenil , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Leucemia Mielomonocítica Juvenil/terapia , Glicoproteína Mielina-Oligodendrócito , Fiebre , Autoanticuerpos
6.
J Hum Genet ; 68(2): 87-90, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36224263

RESUMEN

Angelman syndrome (AS) is caused by the functional absence of the maternal ubiquitin-protein ligase E3A (UBE3A) gene. Approximately 5% of AS is caused by paternal uniparental disomy of chromosome 15 (UPD(15)pat), most of which is considered to result from monosomy rescue. However, little attention has focused on how UPD(15)pat occurs. We suggest the mitotic nondisjunction mechanism as a cause of UPD(15)pat in a six-year-old patient presenting with distinctive characteristics in line with AS. DNA methylation screening of 15q11-q13 showed a paternal band and a faint maternal band, suggestive of mosaic status. By trio-based microsatellite analysis, we confirmed a large proportion of UPD(15)pat cells and a small proportion of cells of biparental origin. Single nucleotide polymorphism (SNP) microarray revealed isodisomy of the entire chromosome 15. These results suggest that the UPD(15)pat of the patient resulted from mitotic nondisjunction, which may also be the cause of other cases of AS with UPD(15)pat.


Asunto(s)
Síndrome de Angelman , Disomía Uniparental , Humanos , Niño , Disomía Uniparental/genética , Síndrome de Angelman/genética , Polimorfismo de Nucleótido Simple , Metilación de ADN/genética , Análisis por Micromatrices
8.
Sci Rep ; 12(1): 14589, 2022 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-36028527

RESUMEN

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24-35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.


Asunto(s)
Exoma , Enfermedades no Diagnosticadas , Variaciones en el Número de Copia de ADN , Oxidasas Duales , Homocigoto , Humanos , Enfermedades Raras , Disomía Uniparental , Secuenciación del Exoma
9.
Brain Dev ; 43(10): 979-987, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34334244

RESUMEN

BACKGROUND: Brush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain. METHODS: We analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter abnormality. Conventional eight-channel electroencephalograms were recorded at 30, 32, 36, and 40 postmenstrual weeks (PMW). Incidence of brushes was calculated as the sum of brushes from each channel separated by active sleep and quiet sleep. A developmental delay was defined as a developmental quotient of <85 assessed at corrected age of 18 months. White matter abnormalities were evaluated with term-equivalent magnetic resonance imaging. RESULTS: The median incidence of brushes (per minute) in 36 infants at PMW 30, 32, 36, and 40 was 16.4, 20.4, 22.5, and 1.8 during active sleep and 7.5, 10.3, 11.5, and 1.7 during quiet sleep, respectively. Among the 36 infants, 14 infants were diagnosed with developmental delay. Longitudinal trajectories of the incidence of brushes were different between the normal and the delayed development groups. Brushes were observed most frequently at 36 PMW in the delayed development group. The incidence of brushes at 36 PMW was significantly correlated with the severity of white matter abnormalities and negatively correlated with the developmental quotient. CONCLUSION: The incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions.


Asunto(s)
Encefalopatías/fisiopatología , Discapacidades del Desarrollo/fisiopatología , Electroencefalografía , Recien Nacido con Peso al Nacer Extremadamente Bajo/fisiología , Recien Nacido Prematuro/fisiología , Sustancia Blanca/patología , Encefalopatías/diagnóstico por imagen , Encefalopatías/patología , Femenino , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Sustancia Blanca/diagnóstico por imagen
10.
Epilepsy Behav ; 118: 107924, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33838621

RESUMEN

OBJECTIVE: Bacille de Calmette et Guérin (BCG) is a live vaccine for tuberculosis that is administered to all infants in Japan. Adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS) causes immunosuppression and may result in BCG infection after BCG vaccination. We evaluated the safety of ACTH therapy initiated shortly after BCG vaccination. METHODS: We analyzed patients with WS who received ACTH therapy between 2005 and 2018. We evaluated the interval between BCG and ACTH therapy, and the rate of BCG infection during and after ACTH therapy, by retrospective chart review. RESULTS: Seventy-nine patients were included in the analysis. Twenty-three patients received ACTH therapy prior to BCG vaccination. For the remaining 56 patients, the median interval between BCG vaccination and the start of ACTH therapy (BCG-ACTH interval) was 91.5 (range 14-280) days. The BCG-ACTH interval was shorter in patients with unknown than in those with known etiologies. It was <8 weeks in 13 patients (10 with unknown and 3 with known etiologies). The minimum BCG-ACTH interval was 14 days. Six patients with epileptic spasms received BCG vaccinations because physicians did not recognize their seizures. None of the patients developed BCG infection. CONCLUSION: No patients who received ACTH therapy after BCG, even at an interval of 8 weeks, developed BCG infection. The timing of ACTH therapy initiation should be based on the risk of BCG-related adverse events and the adverse effects of any delay.


Asunto(s)
Hormona Adrenocorticotrópica/efectos adversos , Hormona Adrenocorticotrópica/uso terapéutico , Vacuna BCG , Espasmos Infantiles , Vacuna BCG/efectos adversos , Humanos , Lactante , Japón , Estudios Retrospectivos , Espasmos Infantiles/tratamiento farmacológico , Espasmos Infantiles/etiología , Vacunación/efectos adversos
11.
Magn Reson Imaging ; 79: 38-44, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33716113

RESUMEN

The accuracy of brain age estimates from magnetic resonance (MR) images has improved with the advent of deep learning artificial intelligence (AI) models. However, most previous studies on predicting age emphasized aging from childhood to adulthood and old age, and few studies have focused on early brain development in children younger than 2 years of age. Here, we performed brain age estimates based on MR images in children younger than 2 years of age using deep learning. Our AI model, developed with one slice each of raw T1- and T2-weighted images from each subject, estimated brain age with a mean absolute error of 8.2 weeks (1.9 months). The estimates of our AI model were close to those of human specialists. The AI model also estimated the brain age of subjects with a myelination delay as significantly younger than the chronological age. These results indicate that the prediction accuracy of our AI model approached that of human specialists and that our simple method requiring less data and preprocessing facilitates a radiological assessment of brain development, such as monitoring maturational changes in myelination.


Asunto(s)
Aprendizaje Profundo , Adolescente , Inteligencia Artificial , Encéfalo/diagnóstico por imagen , Niño , Preescolar , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Adulto Joven
12.
Brain Dev ; 43(2): 288-293, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32888737

RESUMEN

OBJECTIVE: Although the initial treatment of childhood seizures is important, treatment within an appropriate time window is often difficult in resource-limited areas. This study examined childhood seizure treatment in a rural area in Japan. METHODS: We retrospectively investigated children presenting to Nakatsugawa Municipal General Hospital emergency department between 2015 and 2018. From the hospital database, we identified children who were diagnosed with seizures, epilepsy, or acute infectious encephalitis/encephalopathy or were given benzodiazepines. We considered etiology, seizure duration, and treatment according to the specialties of the doctors providing initial care. RESULTS: We extracted 236 seizure events: 40 initially treated by pediatricians, 16 by a mobile doctor team, and 180 by other doctors. Twenty patients had continuous seizures for longer than 5 min on admission. Two were treated by pediatricians at presentation; it took 4 and 7 min after arrival to stop the seizures. Four were treated by a mobile team, and 14 by other doctors; the median response times were 11.5 (range 3-47) and 19 (range 5-60) min, respectively. All patients treated by pediatricians or mobile doctor teams received intravenous or intramuscular diazepam, whereas 50% of those treated by other doctors initially received diazepam suppositories. In three of the 20 events, establishing intravenous access was difficult. SIGNIFICANCE: In rural Japan, many children with seizures are initially treated by doctors other than pediatricians or emergency physicians, and they require a longer time to achieve seizure cessation. Non-intravenous benzodiazepine formulas, which have not yet been approved in Japan, would be helpful.


Asunto(s)
Servicios Médicos de Urgencia/métodos , Accesibilidad a los Servicios de Salud/tendencias , Convulsiones/tratamiento farmacológico , Adolescente , Anticonvulsivantes/uso terapéutico , Benzodiazepinas/administración & dosificación , Benzodiazepinas/uso terapéutico , Niño , Preescolar , Diazepam/uso terapéutico , Servicios Médicos de Urgencia/tendencias , Servicio de Urgencia en Hospital/tendencias , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Japón , Masculino , Estudios Retrospectivos , Población Rural , Estado Epiléptico/tratamiento farmacológico
13.
Neuroradiology ; 63(5): 761-768, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33205317

RESUMEN

PURPOSE: Brain MRI provides important information about suspected congenital CMV infection in neonatally underdiagnosed children. This study aimed to describe MRI findings in children in whom congenital CMV infection was not suspected during the neonatal period and was proven retrospectively. METHODS: We enrolled 31 children referred to the pediatric neurology clinic with neurological symptoms who were proven to have congenital CMV infection based on dried umbilical cord samples. Upon diagnosis, MR and CT images were assessed using the van der Knaap scoring system integrated with additional variables. Two investigators independently assessed all images. RESULTS: The age at diagnosis was < 12 months in 14, 12-24 months in 11, and > 24 months in 6 patients. The initial symptom triggering clinic referral was delayed development in 22, seizure in 5, deafness in 3, and hemiplegia in 1 patient. Of the 31 children, 30 had a white matter (WM) abnormality predominant in the deep WM of the parietal lobe (n = 25). Anterior temporal lesions were observed in 21 children. Cortical lesions were observed in 7 children, suggestive of polymicrogyria. No child had cerebellar or brainstem abnormalities. Brain CT was performed in 22 of 31 children, and 11 showed punctate cerebral calcification in the periventricular and/or deep WM. CONCLUSION: Patients with congenital CMV infection with delayed neurological symptoms show a relatively uniform pattern of parietal-dominant multifocal WM lesions and anterior temporal lesions, with or without polymicrogyria.


Asunto(s)
Infecciones por Citomegalovirus , Sustancia Blanca , Niño , Infecciones por Citomegalovirus/diagnóstico por imagen , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Estudios Retrospectivos , Cordón Umbilical/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen
14.
Neurosci Lett ; 470(2): 134-8, 2010 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-20045719

RESUMEN

Dystrobrevin binding protein-1 gene (DTNBP1), which encodes dysbindin protein, has been identified as a schizophrenia susceptibility gene. Dysbindin has been shown to contribute to the regulation of exocytosis and formation of synaptic vesicles. Although hypofrontality in schizophrenia underlies its pathophysiology, the molecular function of dysbindin in synaptic neurotransmission remains unclear. In the present study, we investigated depolarization-evoked dopamine (DA) and serotonin (5-HT) release in the prefrontal cortex (PFC) of sandy (sdy) mice, which have a deletion mutation in the gene encoding DTNBP1. In vivo microdialysis analysis revealed that extracellular DA levels in the PFC of wild-type mice were increased by 60mM KCl stimulation, and the KCl-evoked DA release was significantly decreased in sdy mice compared with wild-type mice. Extracellular 5-HT levels in the PFC of wild-type mice were also increased by 60mM KCl stimulation. The KCl-evoked 5-HT release did not differ between wild-type and sdy mice. There was no difference in basal levels of DA and 5-HT before the stimulation between two groups. Behavioral sensitization after repeated methamphetamine (METH) treatment was significantly reduced in sdy mice compared with wild-type mice whereas no difference was observed in METH-induced hyperlocomotion between two groups. These results suggest that dysbindin may have a role in the regulation of depolarization-evoked DA release in the PFC and in the development of behavioral sensitization induced by repeated METH treatment.


Asunto(s)
Proteínas Portadoras/metabolismo , Dopamina/metabolismo , Corteza Prefrontal/metabolismo , Animales , Proteínas Portadoras/genética , Cateterismo , Fármacos del Sistema Nervioso Central/farmacología , Dopaminérgicos/farmacología , Disbindina , Proteínas Asociadas a la Distrofina , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Metanfetamina/farmacología , Ratones , Ratones Endogámicos DBA , Microdiálisis , Actividad Motora/efectos de los fármacos , Cloruro de Potasio/farmacología , Corteza Prefrontal/efectos de los fármacos , Eliminación de Secuencia , Serotonina/metabolismo
15.
Neurosci Res ; 64(3): 297-305, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19447299

RESUMEN

It has been reported that viral infection in the first and second trimesters of pregnancy in humans increases the risk of subsequently developing schizophrenia. To develop a mouse model of immune activation during the early postnatal period, neonatal ICR mice were repeatedly injected with polyriboinosinic-polyribocytidilic acid (polyI:C; an inducer of strong innate immune responses) for 5 days (postnatal day 2-6) which may correspond, in terms of brain development, to the early second trimester in human. Cognitive and emotional behavior as well as the extracellular level of glutamate in the hippocampus were analyzed at the age of 10-12 weeks old. PolyI:C-treated mice showed anxiety-like behavior, impairment of object recognition memory and social behavior, and sensorimotor gating deficits, as compared to the saline-treated control group. Depolarization-evoked glutamate release in the hippocampus was impaired in polyI:C-treated mice compared to saline-treated control mice. Furthermore, to investigate the effect of neonatal immune activation on the expression levels of schizophrenia-related genes, we analyzed mRNA levels in the hippocampus 2 and 24h after polyI:C treatment. No significant differences or only transient and marginal changes were observed between polyI:C-treated and saline-treated control mice in the expression levels of schizophrenia-related genes in the hippocampus.


Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/embriología , Polinucleótidos/administración & dosificación , Efectos Tardíos de la Exposición Prenatal/inmunología , Esquizofrenia/inmunología , Animales , Animales Recién Nacidos , Ansiedad/tratamiento farmacológico , Ansiedad/inmunología , Encéfalo/fisiología , Modelos Animales de Enfermedad , Femenino , Expresión Génica/efectos de los fármacos , Ácido Glutámico/metabolismo , Humanos , Memoria/efectos de los fármacos , Ratones , Actividad Motora/efectos de los fármacos , Actividad Motora/inmunología , Polinucleótidos/inmunología , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Filtrado Sensorial/efectos de los fármacos , Filtrado Sensorial/inmunología , Conducta Social
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