Genome sequencing provides high diagnostic yield and new etiological insights for intellectual disability and developmental delay.

Short-read genome sequencing (GS) is a powerful technique for investigating the genetic etiologies of rare diseases, capturing diverse genetic variations that are challenging to approach with exome sequencing (ES). We performed GS on 260 families with intellectual disability/developmental delay. GS detected potentially disease-related variants in 55 of the 260 families, with structural resolution by long-read sequencing or optical genome mapping, and functional assessment by RNA sequencing.

National study on pediatric acute encephalopathy in Japan (April 2020 to October 2023): Insights from the third study.

Background: Previous national studies of acute encephalopathy in Japan were conducted in 2007-2010 and 2014-2017. In this third study (April 1, 2020-October 31, 2023), spanning the coronavirus disease 2019 (COVID-19) outbreak, we compared results to assess trends in pediatric viral infections and therapeutic practices.

Methods: Questionnaires were sent to 430 hospitals of the Japanese Pediatric Society, yielding 241 responses and 1197 cases.

Magnetic resonance imaging and spectroscopy in hypomyelinating leukodystrophy.

Recent advancements in molecular biology and radiology have led to the identification of several new leukodystrophies. A key diagnostic feature of leukodystrophies is the increased white matter signal intensity observed on T2-weighted magnetic resonance (MR) images. Leukodystrophies are typically classified into two main categories: hypomyelinating leukodystrophies (HLD) and other forms, including demyelinating leukodystrophies.

Potential Role of Perampanel in Reducing Barbiturate Dependency in Febrile Infection-Related Epilepsy Syndrome: A Case Report.

Febrile infection-related epilepsy syndrome (FIRES) is a type of new-onset refractory status epilepticus (NORSE) that occurs in previously healthy children. Conventional antiepileptic drugs (AEDs) often fail to control seizures, necessitating the use of high-dose anesthetics, which can lead to severe complications and poor outcomes. Perampanel has shown promise in the treatment of refractory epilepsy; however, its role in FIRES remains underexplored.

Evidence-based diagnostic prediction score for pediatric NMDA receptor encephalitis.

Objective: Early diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) are crucial for a favorable prognosis. Detecting the causative autoantibodies can be challenging. Probable diagnostic criteria are useful in adults less so in children.

Factors influencing the development of infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion.

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.

Clinical characteristics of SARS-CoV-2-associated encephalopathy in children: Nationwide epidemiological study.

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.

An Open-Label Administration of Bioavailable-Form Curcumin in Patients With Pelizaeus-Merzbacher Disease.

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).

A Brain Morphometry Study with Across-Site Harmonization Using a ComBat-Generalized Additive Model in Children and Adolescents.

Regional anatomical structures of the brain are intimately connected to functions corresponding to specific regions and the temporospatial pattern of genetic expression and their functions from the fetal period to old age. Therefore, quantitative brain morphometry has often been employed in neuroscience investigations, while controlling for the scanner effect of the scanner is a critical issue for ensuring accuracy in brain morphometric studies of rare orphan diseases due to the lack of normal reference values available for multicenter studies. This study aimed to provide across-site normal reference values of global and regional brain volumes for each sex and age group in children and adolescents.

Neuroimaging in acute infection-triggered encephalopathy syndromes.

Acute encephalopathy associated with infectious diseases occurs frequently in Japanese children (400-700 children/year) and is the most common in infants aged 0-3 years. Acute encephalopathy is classified into several clinicoradiological syndromes; acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype, followed by clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and acute necrotizing encephalopathy (ANE). Neuroimaging, especially magnetic resonance imaging (MRI), is useful for the diagnosis, assessment of treatment efficacy, and evaluation of the pathophysiology of encephalopathy syndromes.

Neurochemistry evaluated by magnetic resonance spectroscopy in a patient with FBXO28-related developmental and epileptic encephalopathy.

Background: Mutations in the FBXO28 gene, which encodes FBXO28, one of the F-box protein family, may cause developmental and epileptic encephalopathy (DEE). FBXO28-related DEE is radiologically characterized by cerebral atrophy, delayed/abnormal myelination, and brain malformation; however, no neurochemical analyses have been reported.

Case Report: A female Japanese infant presented with severe psychomotor delay, epileptic spasms, and visual impairment.

Prognostic factors among patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome: A retrospective cohort study using a nationwide inpatient database in Japan.

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.

Multimodal MR imaging in acute exacerbation of methylmalonic acidemia.

Methylmalonic acidemia (MMA) is a disorder of methylmalonic acid metabolism caused by impaired methylmalonyl CoA mutase. Neuroimaging shows symmetric hypodensity on CT, and T2 prolongation on MRI in the globus pallidus; however, there have been only a few reports on MR spectroscopy findings and no previous reports on arterial spin labeling (ASL), both of which could reflect neurochemical derangement in MMA. We herein report an 18-month-old Sri Lankan boy presented with severe acute exacerbation of MMA due to bacteremia of O7.