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AIM: To develop standardized diagnostic criteria for 'infection-triggered encephalopathy syndrome (ITES)' and five specific clinical syndromes of ITES. METHOD: The draft definitions were based on existing criteria, standardized, and discussed by a panel of international experts using nominal group technique over 18 months to achieve consensus. All criteria use the same format: (1) presence of infection/fever; (2) clinical features including encephalopathy; (3) neuroradiological features on magnetic resonance imaging; (4) exclusion of other causes. RESULTS: We first highlighted differences between ITES and infectious and autoimmune encephalitis, which is the most important differential diagnosis. Consensus was achieved to define five specific ITESs: acute encephalopathy with biphasic seizures and late reduced diffusion; acute necrotizing encephalopathy; mild encephalopathy with a reversible splenial lesion; acute fulminant cerebral oedema; and acute shock with encephalopathy and multiorgan failure. Two further conditions that are currently classified as epilepsy syndromes but have similar features to ITES, namely febrile infection-related epilepsy syndrome and hemiconvulsion-hemiplegia-epilepsy syndrome, are also discussed. INTERPRETATION: The consensus definition is expected to improve awareness of this disease concept, provide diagnostic framework, and facilitate future international research and clinical trials.
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INTRODUCTION: Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic uremic syndrome (STEC-HUS). Understanding its prognostic factors is essential for immediate interventions. We examined early-phase unfavorable prognostic factors among patients with STEC-HUS using a nationwide database. MATERIAL AND METHODS: This is a retrospective cohort study to analyze practice patterns and identify prognostic factors among patients with STEC-HUS. We used the Diagnosis Procedure Combination Database, which includes approximately half of the acute-care hospitalized patients in Japan. We enrolled patients who were hospitalized for STEC-HUS from July 2010 to March 2020. The composite unfavorable outcome included in-hospital death, mechanical ventilation, dialysis, and rehabilitation at discharge. Unfavorable prognostic factors were assessed using a multivariable logistic regression model. RESULTS: We included 615 patients with STEC-HUS (median age, 7 years). Of them, 30 (4.9%) patients had acute encephalopathy and 24 (3.9%) died within 3 months of admission. Unfavorable composite outcome was observed in 124 (20.2%) patients. Significant unfavorable prognostic factors were age of 18 years or older, methylprednisolone pulse therapy, antiepileptic drug administration, and respiratory support within 2 days of admission. DISCUSSION: Patients requiring early steroid pulse therapy, antiepileptic drugs, and respiratory support were considered to be in poor general condition; such patients should receive aggressive intervention to avoid worse outcomes.
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Infecciones por Escherichia coli , Síndrome Hemolítico-Urémico , Escherichia coli Shiga-Toxigénica , Humanos , Niño , Adolescente , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/diagnóstico , Pacientes Internos , Pronóstico , Estudios Retrospectivos , Japón/epidemiología , Mortalidad Hospitalaria , Síndrome Hemolítico-Urémico/epidemiología , Síndrome Hemolítico-Urémico/terapia , Síndrome Hemolítico-Urémico/diagnósticoRESUMEN
BACKGROUND: Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear. METHODS: We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail. RESULTS: Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly. CONCLUSIONS: Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.
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Colágeno Tipo IV/genética , Mutación/genética , Síndrome de Dandy-Walker/genética , Femenino , Humanos , Masculino , Embarazo , Ultrasonografía Prenatal/métodosRESUMEN
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a pathogen of major importance in pediatric patients. CA-MRSA can cause skin and soft tissue infection in children and young active adults with no predisposing factors, and life-threatening infections such as meningitis or necrotizing pneumonia have been reported. We report here a case of CA-MRSA meningitis complicated by acute left middle cerebral artery (MCA) infarction and necrotizing pneumonia in a previously healthy 1-month-old Vietnamese boy. He was firstly treated with vancomycin, but changed to linezolid because of persistent fever and low vancomycin trough level. He recovered successfully with residual right-sided hemiparesis. The mode of transmission of CA-MRSA and the mechanism of cerebral infarction (thrombotic or embolic) were unknown. The isolate was genotyped as staphylococcal cassette chromosome (SCC) mec type V with a novel sequence type (ST) 5959 harboring the Panton-Valentine leukocidin (PVL) gene. ST 5959 is a double locus variant of ST 59, which is a major PVL-positive CA-MRSA strain isolated in invasive disease in Asian countries. This case report may serve as a warning about the dissemination of PVL-positive CA-MRSA in and around Japan, with the possibility of causing serious life-threatening disease. The potential of linezolid for the treatment of MRSA meningitis as one of the alternative MRSA therapeutic drugs is also discussed.
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Infecciones Comunitarias Adquiridas , Meningitis , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Adulto , Asia , Toxinas Bacterianas , Infarto Cerebral/complicaciones , Infarto Cerebral/tratamiento farmacológico , Niño , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Exotoxinas/genética , Humanos , Lactante , Japón , Leucocidinas/genética , Masculino , Staphylococcus aureus Resistente a Meticilina/genética , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
BACKGROUND: Human parechovirus (HPeV) and human non-polio enterovirus (EV) are important causes of fever without source (FWS) in young infants. Their prevalence and clinical characteristics are largely unknown in Asian countries. This study was conducted to elucidate the epidemiology and clinical characteristics of HPeV and EV infection in febrile young infants in Japan. METHODS: During February 2010-August 2015, we obtained 53 stool, 44 throat swab, and 20 cerebrospinal fluid samples from 56 infants (<3 months) with FWS at a single hospital. To each sample, we applied reverse transcription-polymerase chain reaction for HPeV and EV. We compared the clinical characteristics of HPeV and EV patients. RESULTS: HPeV was detected in 11 and EV in 17 patients. HPeV was detected during July-September. HPeV patients, compared with EV patients, had lower age (32 vs 47 days; P = n.s.), higher prevalence of exclusive breast-feeding (81.8 vs 29.4%; P = 0.024), and lower prevalence of sick contacts (36.4 vs 88.2%; P = 0.010). More HPeV than EV patients met the systemic inflammatory response syndrome criteria (90.9 vs 52.9%; P = 0.049). In the HPeV group, leukopenia, thrombopenia, and elevated deviation enzyme were observed, although the prevalence of abnormal cerebrospinal fluid was significantly lower than in the EV group. HPeV patients had longer hospital stay (7 vs 5 days; P = 0.025). CONCLUSION: HPeV and EV are important causal viruses of FWS. Characteristic clinical pictures exist in these virus infections, but further research is needed to accumulate more cases to produce a comprehensive picture of these virus infections.
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Infecciones por Enterovirus/epidemiología , Enterovirus/aislamiento & purificación , Parechovirus/aislamiento & purificación , Infecciones por Picornaviridae/epidemiología , Líquido Cefalorraquídeo/microbiología , Infecciones por Enterovirus/diagnóstico , Heces/microbiología , Femenino , Fiebre/etiología , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Masculino , Faringe/microbiología , Infecciones por Picornaviridae/diagnóstico , Prevalencia , Estudios Prospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Leukoencephalopathy with brain calcifications and cysts (LCC) is neuroradiologically characterized by leukoencephalopathy, intracranial calcification, and cysts. Coats plus syndrome is also characterized by the same neuroradiological findings together with defects in retinal vascular development. Indeed, LCC and Coats plus were originally considered to be the same clinical entity termed cerebroretinal microangiopathy with calcifications and cysts, but evidence suggests that they are genetically distinct. Mutations in CTS telomere maintenance complex component 1 (CTC1) and small nucleolar RNA, C/D box 118 (SNORD118) genes have been found to cause Coats plus and LCC, respectively. MATERIALS AND METHODS: Eight unrelated families with LCC were recruited. These patients typically showed major neuroradiological findings of LCC with no signs of extra-neurological manifestations such as retinal abnormality, gastrointestinal bleeding, or hematological abnormalities. SNORD118 was examined by Sanger sequencing in these families. RESULTS: Seven out of eight probands carry compound heterozygous mutations, suggesting that SNORD118 mutations are the major cause of LCC. We identified a total of eight mutation, including four that were novel. Some of the variants identified in this study present heterozygously in public databases with an extremely rare frequency (<0.1%). CONCLUSION: Biallelic SNORD118 mutations were exclusively found in most unrelated families with LCC.
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Calcinosis/genética , Quistes del Sistema Nervioso Central/genética , Predisposición Genética a la Enfermedad , Leucoencefalopatías/genética , ARN Nucleolar Pequeño/genética , Adulto , Alelos , Encéfalo/fisiopatología , Calcinosis/epidemiología , Calcinosis/fisiopatología , Quistes del Sistema Nervioso Central/epidemiología , Quistes del Sistema Nervioso Central/fisiopatología , Quistes/genética , Bases de Datos Factuales , Femenino , Heterocigoto , Humanos , Leucoencefalopatías/epidemiología , Leucoencefalopatías/fisiopatología , Masculino , Mutación , Proteínas de Unión a Telómeros/genéticaRESUMEN
INTRODUCTION: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. It is sometimes difficult to make an early diagnosis of AESD; excitotoxicity is postulated to be the pathogenesis based on elevated glutamine (Gln) and glutamate (Glu) complex (Glx = Glu + Gln) observed on MR spectroscopy. It is uncertain whether Gln or Glu contributes to the elevated Glx, or whether MR spectroscopy is useful for an early diagnosis. METHODS: Five Japanese patients with AESD (three boys and two girls, 1 year of age) were enrolled in this study. MR spectroscopy was acquired from the frontal white matter (repetition time (TR) of 5000 ms, echo time (TE) of 30 ms) with a 1.5- or 3.0-T scanner. MR spectroscopy was performed four times for two patients, three times for one patient, and two times for two patients. Quantification of Glu and Gln was performed using LCModel. RESULTS: Glu was elevated in three of four studies on days 1-4 and became normal or low afterward. Gln was normal in three studies on days 1-2, elevated in all seven studies on days 4-12, and became normal or low afterward. CONCLUSION: These findings suggest that MR spectroscopy may be useful for an early diagnosis. Acute Glu elevation changes to subacute Gln elevation, suggesting that a disrupted Glu-Gln cycle may play an important role.
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Epilepsia Tónico-Clónica/metabolismo , Lóbulo Frontal/metabolismo , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Sustancia Blanca/metabolismo , Biomarcadores/sangre , Epilepsia Tónico-Clónica/patología , Femenino , Lóbulo Frontal/patología , Humanos , Recién Nacido , Masculino , Tasa de Depuración Metabólica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución Tisular , Sustancia Blanca/patologíaRESUMEN
Oral-facial-digital syndrome type VI (OFD VI) is a recessive ciliopathy defined by two diagnostic criteria: molar tooth sign (MTS) and one or more of the following: (1) tongue hamartoma (s) and/or additional frenula and/or upper lip notch; (2) mesoaxial polydactyly of one or more hands or feet; (3) hypothalamic hamartoma. Because of the MTS, OFD VI belongs to the "Joubert syndrome related disorders". Its genetic aetiology remains largely unknown although mutations in the TMEM216 gene, responsible for Joubert (JBS2) and Meckel-Gruber (MKS2) syndromes, have been reported in two OFD VI patients. To explore the molecular cause(s) of OFD VI syndrome, we used an exome sequencing strategy in six unrelated families followed by Sanger sequencing. We identified a total of 14 novel mutations in the C5orf42 gene in 9/11 families with positive OFD VI diagnostic criteria including a severe fetal case with microphthalmia, cerebellar hypoplasia, corpus callosum agenesis, polydactyly and skeletal dysplasia. C5orf42 mutations have already been reported in Joubert syndrome confirming that OFD VI and JBS are allelic disorders, thus enhancing our knowledge of the complex, highly heterogeneous nature of ciliopathies.
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Proteínas de la Membrana/genética , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Anomalías Múltiples , Adolescente , Adulto , Alelos , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/genética , Cerebelo/anomalías , Niño , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Exoma , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Femenino , Hamartoma/diagnóstico , Hamartoma/genética , Humanos , Enfermedades Hipotalámicas/diagnóstico , Enfermedades Hipotalámicas/genética , Enfermedades Renales Quísticas/diagnóstico , Enfermedades Renales Quísticas/genética , Masculino , Mutación , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/genética , Fenotipo , Polidactilia/diagnóstico , Polidactilia/genética , Retina/anomalías , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Congenital hypomyelinating disorders are a heterogeneous group of inherited leukoencephalopathies characterized by abnormal myelin formation. We have recently reported a hypomyelinating syndrome characterized by diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). We performed whole-exome sequencing of three unrelated individuals with HCAHC and identified compound heterozygous mutations in POLR3B in two individuals. The mutations include a nonsense mutation, a splice-site mutation, and two missense mutations at evolutionally conserved amino acids. Using reverse transcription-PCR and sequencing, we demonstrated that the splice-site mutation caused deletion of exon 18 from POLR3B mRNA and that the transcript harboring the nonsense mutation underwent nonsense-mediated mRNA decay. We also identified compound heterozygous missense mutations in POLR3A in the remaining individual. POLR3A and POLR3B encode the largest and second largest subunits of RNA Polymerase III (Pol III), RPC1 and RPC2, respectively. RPC1 and RPC2 together form the active center of the polymerase and contribute to the catalytic activity of the polymerase. Pol III is involved in the transcription of small noncoding RNAs, such as 5S ribosomal RNA and all transfer RNAs (tRNA). We hypothesize that perturbation of Pol III target transcription, especially of tRNAs, could be a common pathological mechanism underlying POLR3A and POLR3B mutations.
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Codón sin Sentido , Predisposición Genética a la Enfermedad/genética , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/genética , Mutación Missense , ARN Polimerasa III/genética , Adolescente , Adulto , Secuencia de Bases , Cuerpo Calloso/patología , Exoma/genética , Femenino , Genes Recesivos/genética , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/patología , Humanos , Masculino , Modelos Moleculares , Datos de Secuencia Molecular , Degradación de ARNm Mediada por Codón sin Sentido/genética , Linaje , Sitios de Empalme de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations. METHODS: We screened for COL4A1 mutations in 61 patients with porencephaly and 10 patients with schizencephaly, which may be similarly caused by disturbed vascular supply leading to cerebral degeneration, but can be distinguished depending on time of insult. RESULTS: COL4A1 mutations were identified in 15 patients (21%, 10 mutations in porencephaly and 5 mutations in schizencephaly), who showed a variety of associated findings, including intracranial calcification, focal cortical dysplasia, pontocerebellar atrophy, ocular abnormalities, myopathy, elevated serum creatine kinase levels, and hemolytic anemia. Mutations include 10 missense, a nonsense, a frameshift, and 3 splice site mutations. Five mutations were confirmed as de novo events. One mutation was cosegregated with familial porencephaly, and 2 mutations were inherited from asymptomatic parents. Aberrant splicing was demonstrated by reverse transcriptase polymerase chain reaction analyses in 2 patients with splice site mutations. INTERPRETATION: Our study first confirmed that COL4A1 mutations are associated with schizencephaly and hemolytic anemia. Based on the finding that COL4A1 mutations were frequent in patients with porencephaly and schizencephaly, genetic testing for COL4A1 should be considered for children with these conditions.
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Encefalopatías/genética , Colágeno Tipo IV/genética , Hemiplejía/genética , Malformaciones del Desarrollo Cortical/genética , Mutación/genética , Fenotipo , Anemia Hemolítica/genética , Anemia Hemolítica/patología , Encefalopatías/patología , Niño , Preescolar , Colágeno Tipo IV/deficiencia , Hemiplejía/patología , Humanos , Lactante , Malformaciones del Desarrollo Cortical/patología , PorencefaliaRESUMEN
PURPOSE: To evaluate the neurochemical changes associated with hypomyelination, especially to clarify whether increased total N-acetylaspartate (tNAA) with decreased choline (Cho) observed in the thalamus of msd mice with the plp1 mutation is a common finding for hypomyelinating disorders. MATERIALS AND METHODS: We performed magnetic resonance imaging (MRI) and proton MR spectroscopy ((1) H-MRS) of the thalamus and cortex of postnatal 12-week shiverer mice devoid of myelin basic protein (mbp), heterozygous and wild-type mice with a 7.0T magnet. Luxol Fast Blue staining and immunohistochemical analysis with anti-Mbp, Gfap, Olig2, and NeuN antibodies were also performed. RESULTS: In the thalamus, decreased Cho and normal tNAA were observed in shiverer mice. In the cortex, tNAA, Cho, and glutamate were decreased in shiverer mice. Histological and immunohistochemical analysis of shiverer mice brains revealed hypomyelination in the thalamus, white matter, and cortex; astrogliosis and an increased number of total oligodendrocytes in the white matter; and a decreased number of neurons in the cortex. CONCLUSION: The reduction of Cho on (1) H-MRS might be a common marker for hypomyelinating disorders. A normal tNAA level in the thalamus of shiverer mice might be explained by the presence of mature oligodendrocytes, which enable neuron-to-oligodendrocyte NAA transport or NAA catabolism.
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Sistemas de Transporte de Aminoácidos Acídicos/deficiencia , Antiportadores/deficiencia , Ácido Aspártico/análogos & derivados , Encéfalo/metabolismo , Colina/metabolismo , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Enfermedades Mitocondriales/metabolismo , Trastornos Psicomotores/metabolismo , Sistemas de Transporte de Aminoácidos Acídicos/metabolismo , Análisis de Varianza , Animales , Antiportadores/metabolismo , Ácido Aspártico/metabolismo , Encéfalo/patología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Modelos Animales de Enfermedad , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/patología , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Endogámicos ICR , Ratones Mutantes Neurológicos , Enfermedades Mitocondriales/patología , Proteína Básica de Mielina/metabolismo , Neuroquímica/métodos , Trastornos Psicomotores/patología , Tálamo/metabolismo , Tálamo/patología , Sustancia Blanca/metabolismo , Sustancia Blanca/patologíaRESUMEN
MRI and CT are important for the diagnosis and treatment of epilepsy. Diffusion-weighted images are particularly useful for detecting early changes in the brain. In this article, I reviewed radiological findings associated with seizures (reduced diffusion and swelling of hippocampus and cortex, and a reversible splenial lesion), and lesions causing epilepsy and seizures, such as congenital abnormality of the brain (holoprosencephaly, hemimegalencephaly, lissencephaly, heterotopia, polymicrogyria, schizencephaly, and focal cortical dysplasia), neurocutaneous syndromes (tuberous sclerosis and Sturge-Weber syndrome), vascular disorders (moyamoya disease/syndrome and cavernous angioma), and encephalitis/encephalopathy (herpes encephalitis, anti-NMDA receptor encephalitis, acute necrotizing encephalopathy of childhood, and acute encephalopathy with biphasic seizures and late reduced diffusion).
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Encefalopatías/complicaciones , Encefalopatías/diagnóstico , Epilepsia/diagnóstico , Epilepsia/etiología , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encefalopatías/patología , Niño , Preescolar , Epilepsia/patología , Femenino , Humanos , Lactante , MasculinoRESUMEN
In this article, we report the third case of chloride voltage-gated channel 2 (CLCN2)-related leukoencephalopathy (CC2L) in Japan. The patient presented with headache, vertigo, and mild visual impairment. The CLCN2 variant of the patient, NM_004366.6:c.61dup, p.(Leu21Profs*27), was also found in two other Japanese patients as this variant is relatively common in the Japanese population. Magnetic resonance imaging (MRI) revealed T2 prolongation with reduced diffusion in the bilateral posterior limbs of the internal capsule, cerebral peduncles, and superior and middle cerebellar peduncles. Magnetic resonance spectroscopy (MRS) of normal-appearing white matter revealed decreased choline content. This represents the first evidence of decreased choline levels in CC2L, highlighting the superior sensitivity of MRS over MRI.
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BACKGROUND: Two preclinical studies using mouse models of Pelizeaus-Merzbacher disease (PMD) have revealed the potential therapeutic effects of curcumin. In this study, we examined the effects of curcumin in patients with PMD. METHODS: We conducted a study administering an open-label oral bioavailable form of curcumin in nine patients genetically confirmed to have PMD (five to 20 years; mean 11 years) for 12 months (low doses for two months followed by high doses for 10 months). We evaluated changes in clinical symptoms as the primary end point using two scales, Gross Motor Function Measure (GMFM) and the PMD Functional Disability Score (PMD-FDS). The level of myelination by brain magnetic resonance imaging (MRI) and the electrophysiological state by auditory brainstem response (ABR) were evaluated as secondary end points. The safety and tolerability of oral curcumin were also examined. RESULTS: Increase in GMFM and PMD-FDS were noted in five and three patients, respectively, but overall, no statistically significant improvement was demonstrated. We found no clear improvement in their brain MRI or ABR. No adverse events associated with oral administration of curcumin were observed. CONCLUSIONS: Although we failed to demonstrate any significant therapeutic effects of curcumin after 12 months, its tolerability and safety were confirmed. This study does not exclude the possibility of therapeutic effects of curcumin, and a trial of longer duration should be considered to compare the natural history of the disease with the effects of curcumin.
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Curcumina , Enfermedad de Pelizaeus-Merzbacher , Animales , Ratones , Humanos , Enfermedad de Pelizaeus-Merzbacher/diagnóstico por imagen , Enfermedad de Pelizaeus-Merzbacher/tratamiento farmacológico , Enfermedad de Pelizaeus-Merzbacher/genética , Curcumina/farmacología , Curcumina/uso terapéutico , Encéfalo/patología , Imagen por Resonancia Magnética , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Proteína Proteolipídica de la MielinaRESUMEN
BACKGROUND: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has been reported as a type of TBI. However, it remains uncertain which pediatric patients with TBI develop TBIRD. METHODS: Patients with TBI who were admitted to our hospital and underwent magnetic resonance imaging (MRI) between December 2006 and October 2022 were included in this study. A diagnosis of TBIRD was made in patients with or suspected TBI, with initial symptoms being convulsions or disturbance of consciousness and late-onset subcortical reduced diffusion, the so-called bright tree appearance. Clinical features, neuroimaging (computed tomography (CT) and MRI) findings, laboratory data, and Tada score were retrospectively compared between TBIRD and non-TBIRD patients. Neurological prognosis was assessed using the Pediatric Cerebral Performance Category scale. RESULTS: Of 21 patients who met the inclusion criteria, a diagnosis of TBIRD was made in 7 patients (median age: 8 months). The factors contributing to TBIRD development were seizures lasting over 30 min as the initial symptom (5/7 in TBIRD vs. 0/14 in non-TBIRD), tracheal intubation during initial treatment (5/7 vs. 0/14), and brain parenchymal lesions on CT (3/7 vs. 0/14), suggesting that severe TBI may progress to TBIRD. The Tada score was more positive in patients with TBIRD (6/7) than in those without (0/14). CONCLUSIONS: It is important to monitor infant patients with severe TBI for the development of TBIRD. The Tada score can be a useful tool for TBIRD prediction.
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Lesiones Traumáticas del Encéfalo , Convulsiones , Lactante , Humanos , Niño , Estudios Retrospectivos , Convulsiones/diagnóstico , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Progresión de la EnfermedadRESUMEN
OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sometimes triggers acute encephalopathy as a serious neurological complication in children. We previously reported the clinico-radiological findings of SARS-CoV-2-associated encephalopathy. The advent of the SARS-CoV-2 omicron variant led to a marked increase in pediatric patients with coronavirus disease 2019 (COVID-19); however, epidemiological changes with acute encephalopathy according to the emergence of SARS-CoV-2 have not yet been documented. Therefore, the present study investigated epidemiological differences in SARS-CoV-2-associated encephalopathy during the BA.1/BA.2 and BA.5 predominant periods and also between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. METHODS: We conducted a nationwide survey of SARS-CoV-2-associated encephalopathy in Japanese children between June and November 2022. We compared the present results during the BA.5 predominant period and previous findings during the BA.1/BA.2 predominant period. We also compared the clinico-radiological syndromes of encephalopathy between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. RESULTS: Although many patients with SARS-CoV-2-associated encephalopathy in the BA.5 predominant period had seizures as their initial symptoms, no significant differences were observed in the clinical features. Patients with SARS-CoV-2-associated encephalopathy had worse outcomes than those with non-SARS-CoV-2-associated encephalopathy (p-value = 0.003). Among 103 patients with SARS-CoV-2-associated encephalopathy, 14 (13.6%) had severe types of acute encephalopathy, namely, encephalopathy with acute fulminant cerebral edema (AFCE) and hemorrhagic shock and encephalopathy syndrome (HSES). Also, 28 (27.2%) patients with SARS-CoV-2-associated encephalopathy had poor outcome: severe neurological sequelae or death. Ninety-five patients (92.2%) were not vaccinated against SARS-CoV-2. CONCLUSIONS: In SARS-CoV-2-associated encephalopathy, high percentages of AFCE and HSES can result in poor outcomes.
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Trastornos de la Coagulación Sanguínea , Encefalopatías , COVID-19 , Choque Hemorrágico , Humanos , Niño , SARS-CoV-2 , COVID-19/complicaciones , COVID-19/epidemiología , Encefalopatías/diagnóstico por imagen , Encefalopatías/epidemiología , Encefalopatías/etiología , Estudios EpidemiológicosRESUMEN
Kabuki syndrome is a congenital anomaly syndrome characterized by developmental delay, intellectual disability, specific facial features including long palpebral fissures and ectropion of the lateral third of the lower eyelids, prominent digit pads, and skeletal and visceral abnormalities. Mutations in MLL2 and KDM6A cause Kabuki syndrome. We screened 81 individuals with Kabuki syndrome for mutations in these genes by conventional methods (n = 58) and/or targeted resequencing (n = 45) or whole exome sequencing (n = 5). We identified a mutation in MLL2 or KDM6A in 50 (61.7%) and 5 (6.2%) cases, respectively. Thirty-five MLL2 mutations and two KDM6A mutations were novel. Non-protein truncating-type MLL2 mutations were mainly located around functional domains, while truncating-type mutations were scattered through the entire coding region. The facial features of patients in the MLL2 truncating-type mutation group were typical based on those of the 10 originally reported patients with Kabuki syndrome; those of the other groups were less typical. High arched eyebrows, short fifth finger, and hypotonia in infancy were more frequent in the MLL2 mutation group than in the KDM6A mutation group. Short stature and postnatal growth retardation were observed in all individuals with KDM6A mutations, but in only half of the group with MLL2 mutations.