Abnormal theta-band rhythm: EEG abnormality as potential biomarkers for disease severity in pediatric anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children often requires early immunosuppressive therapy before antibody detection. While various electroencephalogram (EEG) patterns, including extreme delta brushes (EDBs), have been reported in adults, pediatric EEG characteristics remain understudied. This study aims to assist clinicians in identifying severe cases early, potentially improving treatment outcomes through prompt intervention.

Exploring unsolved cases of lissencephaly spectrum: integrating exome and genome sequencing for higher diagnostic yield.

Lissencephaly is a rare brain malformation characterized by abnormal neuronal migration during cortical development. In this study, we performed a comprehensive genetic analysis using next-generation sequencing in 12 unsolved Japanese lissencephaly patients, in whom PAFAH1B1, DCX, TUBA1A, and ARX variants were excluded using the Sanger method. Exome sequencing (ES) was conducted on these 12 patients, identifying pathogenic variants in CEP85L, DYNC1H1, LAMC3, and DCX in four patients.

Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy in Children-A Literature Review.

Vagus nerve stimulation (VNS) is a palliative treatment for drug-resistant epilepsy (DRE) that has been in use for over two decades. VNS suppresses epileptic seizures, prevents emotional disorders, and improves cognitive function and sleep quality, a parallel effect associated with the control of epileptic seizures. The seizure suppression rate with VNS increases monthly to annually, and the incidence of side effects reduces over time.

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).

Myelin abnormalities in merosin-deficient congenital muscular dystrophy.

Introduction/aims: Merosin is a protein complex located in the basement membrane of skeletal muscles and laminin α2-containing regions of the central and peripheral nervous systems. However, because of the prominence of muscle-related symptoms, peripheral neuropathy associated with merosin-deficient congenital muscular dystrophy type 1A (MDC1A) has received little clinical attention. This study aimed to present pathological changes in intramuscular nerves of three patients with MDC1A and discuss their relationship with electrophysiological findings to provide new evidence of peripheral nerve involvement in MDC1A.

Long-term Observation in Patients with Duchenne Muscular Dystrophy with Early Introduction of a Standing Program Using Knee-ankle-foot Orthoses.

Objectives: This study investigated the outcomes of the early introduction of a standing program for patients with Duchenne muscular dystrophy (DMD).

Methods: This was a retrospective observational study of 41 outpatients with DMD aged 15-20 years. We introduced the standing program using knee-ankle-foot orthoses (KAFO) to slow the progression of scoliosis when ankle dorsiflexion became less than 0° in the ambulatory period.

Systemic administration of the antisense oligonucleotide NS-089/NCNP-02 for skipping of exon 44 in patients with Duchenne muscular dystrophy: Study protocol for a phase I/II clinical trial.

Aim: The purpose of this study is to evaluate the safety and pharmacokinetics of the novel morpholino oligomer NS-089/NCNP-02 which can induce exon 44 skipping, in patients with DMD. Additionally, we aimed to identify markers predictive of therapeutic efficacy and determine the optimal dosing for future studies.

Methods: This is an open-label, dose-escalation, two-center phase I/II trial in ambulant patients with DMD, presence of an out-of-frame deletion, and a mutation amenable to exon 44 skipping.

[Treatment of Spinal Muscular Atrophy].

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that predominantly affects motor neurons, resulting in progressive muscular atrophy and weakness. SMA arises due to insufficient levels of the survival motor neuron (SMN) protein as a result of homozygous disruption of the SMN1 gene. The SMN protein is also produced by the paralogous gene SMN2, but the amount of SMN produced is minimal due to a defect in the splicing process.

Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy.

Purpose: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects.

Methods: Patients with CBHA in 176 families were genetically examined using exome sequencing.

Long-term changes in electroencephalogram findings in a girl with a nonsense SMC1A variant: A case report.

Introduction: Pathogenic truncating variants in SMC1A, which is located on chromosome Xp11.2, are known to cause infantile-onset epilepsy and severe intellectual disability in girls. Several studies have reported a correlation between SMC1A truncations and seizure clustering; however, the associated electroencephalogram (EEG) patterns remain largely unknown.

A familial 2p14 microdeletion disrupting actin-related protein 2 and Ras-related protein Rab-1A genes with intellectual disability and language impairment.

Microdeletions encompassing the 2p14 region have been reported to cause a novel microdeletion syndrome, characterised by mild intellectual disability (ID) and language impairment (LI), usually showing no congenital malformations or severe dysmorphisms. Actin-related protein 2 (ACTR2) and Ras-related protein Rab-1A (RAB1A) genes present in this region have been suggested to be associated with ID and/or LI pathogenesis on the basis of a few singleton cases with 2p14 microdeletions, although the effects of other deleted genes could not be ruled out. Here, we describe the clinical and molecular cytogenetic characterisation of a three-generation Japanese family comprising six individuals carrying a 144-kb microdeletion at the 2p14 locus, which disrupted two genes, ACTR2 and RAB1A, and co-segregated with ID and LI.

International retrospective natural history study of -related congenital muscular dystrophy.

Muscular dystrophies due to heterozygous pathogenic variants in gene cover a broad spectrum of clinical presentations and severity with an age of onset ranging from the neonatal period to adulthood. The natural history of these conditions is not well defined, particularly in patients with congenital or early onset who arguably present with the highest disease burden. Thus the definition of natural history endpoints along with clinically revelant outcome measures is essential to establishing both clinical care planning and clinical trial readiness for this patient group.

Whole genome sequencing of 45 Japanese patients with intellectual disability.

Intellectual disability (ID) is characterized by significant limitations in both intellectual functioning and adaptive behaviors, originating before the age of 18 years. However, the genetic etiologies of ID are still incompletely elucidated due to the wide range of clinical and genetic heterogeneity. Whole genome sequencing (WGS) has been applied as a single-step clinical diagnostic tool for ID because it detects genetic variations with a wide range of resolution from single nucleotide variants (SNVs) to structural variants (SVs).

Highly sensitive screening of antisense sequences for different types of DMD mutations in patients' urine-derived cells.

Exon skipping using short antisense oligonucleotides (AONs) is a promising treatment for Duchenne muscular dystrophy (DMD). Several exon-skipping drugs, including viltolarsen (NS-065/NCNP-01), have been approved worldwide. Immortalized human skeletal muscle cell lines, such as rhabdomyosarcoma cells, are frequently used to screen efficient oligonucleotide sequences.

Association between lack of functional connectivity of the frontal brain region and poor response inhibition in children with frontal lobe epilepsy.

Purpose: We investigated the relationship between electroencephalographic (EEG) functional connectivity and executive function in children with frontal lobe epilepsy (FLE).

Methods: We enrolled 24 children with FLE (mean age, 11.0 years; 13 boys) and 22 sex-, age-, and intelligence-matched typically developing children (TDC) to undergo 19-channel EEG during light sleep.

Hyperglycemic Crisis in Patients With Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS).

Background: Diabetes mellitus is the most commonly encountered endocrinopathy in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), which manifests as multisystemic organ failure. Whether the management of diabetes mellitus in MELAS requires special consideration is not fully clarified.

Methods: In this single-center study, we retrospectively reviewed the medical records of patients with MELAS to elucidate the clinical characteristics of MELAS-associated diabetes mellitus.

Postoperative improvement of executive function and adaptive behavior in children with intractable epilepsy.

Introduction: An alteration in postoperative cognitive function varies according to the patients' background characteristics, such as etiology, focus, and seizure duration. Accurate prediction and assessment of postoperative cognitive function is difficult in each patient. Adaptive behavior could describe the typical performance of daily activities and represents the ability to translate cognitive potential into real-world skills.

Prenatal clinical manifestations in individuals with variants.

Background: Variants in the type IV collagen gene () cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with variants remain unclear.

Methods: We examined in 218 individuals with suspected /2-related brain defects.

ADSSL1 myopathy is the most common nemaline myopathy in Japan with variable clinical features.

Objective: To elucidate the prevalence of Japanese ADSSL1 myopathy and determine the clinicopathologic features of the disease.

Methods: We searched for variants in myopathic patients from January 1978 to March 2019 in our repository and assessed the clinicopathologic features of patients with variants.

Results: We identified 63 patients from 59 families with biallelic variants of .

13q13.3 microdeletion associated with apparently balanced translocation of 46,XX,t(7;13) suggests NBEA involvement.

Background: Deletion of 13q13.3 is an extremely rare event.

Case: We report on a 25-month-old girl with neurodevelopmental disorder and intellectual disability.