Background Gastrointestinal (GI) difficulties are very common among children with cerebral palsy (CP) and comorbid epilepsy. GI function is influenced by dietary structure on gut microbiota. The aim of this study was to compare gut microbiota differences in two dietary groups of this population and examine whether such differences are related to GI dysfunction. Methods Forty children with CP and epilepsy

Background Reversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum, emerging related to encephalitis, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Among RESLES, mild encephalitis/encephalopathy with reversible splenial lesion (MERS) has been defined as a distinct clinicoradiologic syndrome associated with viral

Background Microcephalic osteodysplastic primordial dwarfism type I (MOPD I, also known as Taybi-Linder syndrome) is a rare genetic disorder associated with severe intrauterine growth retardation, short stature, microcephaly, brain anomalies, stunted limbs, and early mortality. RNU4ATAC, the gene responsible for this disorder, does not encode a protein but instead the U4atac small nuclear RNA (snRNA)

Background Spinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion of SMN1 exons 7 and 8. However, exon 8 is retained in some cases, where SMN2 exon 7 recombines with SMN1 exon 8, forming a hybrid SMN gene. It remains unknown how the hybrid SMN gene contribute to the SMA phenotype. Method We analyzed 515 patients with clinical suspicion for SMA. SMN1 exons 7 and 8 deletion

Background The medical treatment for severe pallid breath-holding spells accompanied with severe bradycardia or transient cardiac arrest is controversial. Although various medications have been reported to be effective, patients treated with pacemaker insertion are not always evaluated for pharmacological therapy beforehand. Case report A 9-month-old boy developed pallid breath-holding spells. At 15 months

Background Measles (rubeola) is a highly contagious infectious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) to prevent measles. This retrospective longitudinal cohort study evaluated childhood MMR vaccination and the risk of a seizure episode and seizure disorder. Methods The Independent Healthcare Research Database

Background Progress in neonatal medicine has dramatically improved the survival rate of preterm births, but the evidence suggests that these low-birth weight infants (LBWIs) go on to develop pervasive development disorders and attention deficit hyperactivity disorder (ADHD) at greater rates than the general population. Children with neurodevelopmental disorders are known to suffer from deficits in

Background Combined oxidative phosphorylation deficiency 35 (COXPD 35) is a very rare autosomal recessive disorder caused by homozygous or compound heterozygous mutations in the TRIT1 gene on chromosome 1p34. Only six cases of COXPD 35 and six allelic variants of TRIT1 gene mutations have been reported worldwide. Case description: We describe two siblings who presented with similar clinical features

Purpose KCNQ2 mutations are associated with benign familial neonatal epilepsy (BFNE) or developmental and epileptic encephalopathy (DEE). In this study, we aimed to delineate the phenotype of KCNQ2 encephalopathy and evaluate the treatment response. Methods Thirteen patients of KCNQ2 encephalopathy were included in the study. Characteristics of KCNQ2 mutations, electroclinical features, clinical course

Background Most children with Benign epilepsy with centro-temporal spikes (BECTS) undergo remission during late adolescence and do not require treatment. In a small group of patients, the condition may evolve to encephalopathic syndromes including epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), or Landau-Kleffner Syndrome (LKS). Development of prediction models for early

Background SCN2A mutations are some of the commonest causes of neurodevelopmental disorders including epilepsy, movement disorders, autism spectrum disorder, intellectual disability and rarely episodic ataxia. Case report We present a patient with a dominantly inherited SCN2A mutation presenting as episodic ataxia in a boy and episodic hemiplegia in his father. We have briefly reviewed the literature

Bell’s palsy is an acute facial paralysis with known association to viral infections. We describe a medically complex 6-year-old male with hyper IgM syndrome who presented with unilateral facial droop and positive SARS-CoV-2 RT-PCR. This is the first reported pediatric case of Bell’s palsy in the setting of SARS-CoV-2 infection.

Background Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive inborn error that affects phenylalanine (Phe) metabolism. It has a complex phenotype with many variants and genotypes among different populations. Shanxi province is a high-prevalence area of PAHD in China. Methods In this study, eighty-nine PAHD patients were subjected to genetic testing using Sanger sequencing, followed

Background We retrospectively evaluated the pathogens in the cerebrospinal fluid (CSF) of pediatric meningitis/encephalitis (M/E) by FilmArray meningitis/encephalitis panel (FA-MEP), and the characteristics of children showing positive and negative FA-MEP results. Method FA-MEP along with conventional tests (bacterial/viral cultures, and polymerase chain reaction tests) was performed in children who

Angelman Syndrome (AS) is characterized by severe developmental delays including marked speech impairment, movement abnormalities(ataxia, tremor), and unique behaviors such as frequent laughter and is caused by dysfunctional maternal UBE3A gene (maternal 15q11-13 deletions, maternal specific UBE3A mutation, uniparental disomy, and imprinting defect). Intractable epileptic seizures since early childhood

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

Background Heterozygous variants in BICD2 cause autosomal dominant spinal muscular atrophy with lower extremity predominance. These variants are also identified in individuals with severe forms of congenital muscle atrophy representing arthrogryposis multiplex. Case report A girl was born with severe muscle weakness and respiratory distress. A fetal ultrasound had detected polyhydramnios and multiple

Introduction Spinal muscular atrophy (SMA) is caused by a defect in the survival motor neuron 1 (SMN1) gene. The Cooperative Study of the natural history of SMA Type I in Taiwan is a retrospective, longitudinal, observational study that helps in further understanding SMA disease progression in patients who have not received disease-modifying therapeutic interventions. Methods Case report forms were

Background and purpose Bottom shuffling is a locomotion strategy that precedes independent walking in some infants. Shuffling babies are generally considered to have favorable outcomes. The aim of the present study was to reveal clinical features and neurodevelopmental outcomes of shuffling babies who visited a child developmental center. Methods We studied 48 shuffling babies who visited Toyota Municipal

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

Introduction Metachromatic leukodystrophy (MLD) refers to leukodystrophy caused by the accumulation of sulfatide from arylsulfatase A (ARSA) gene mutations. Sulfatide also accumulates in various organs, including the peripheral nerves, kidney, and gallbladder. Proliferative changes in the gallbladder have been reported in several patients, while gallbladder cancer is reported in only two adult MLD

Background Infections are a common cause of childhood stroke with variable presentation. The current case describes a rare infective cause of venous and arterial stroke in an immunocompetent girl with management implications. Case description A 12 year old girl, presented with history of fever for 10 days, painful swelling of right eye for 7 days and altered sensorium for 2 days. On examination, she

The cardinal symptom of acute encephalopathy is impairment of consciousness of acute onset during the course of an infectious disease, with duration and severity meeting defined criteria. Acute encephalopathy consists of multiple syndromes such as acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late reduced diffusion and clinically mild encephalitis/encephalopathy

Background The ALDH18A1 gene is located at 10q24.1 and encodes delta-1-pyrroline-5-carboxylate synthetase (P5CS), a mitochondrial bifunctional enzyme that catalyzes the first two steps in de novo biosynthesis of proline, ornithine, citrulline, and arginine. ALDH18A1-related disorders have been classified into four groups, such as autosomal dominant and recessive hereditary spastic paraplegia (SPG9A

Background Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a mitochondrial fatty acid oxidation disorder that causes episodic attacks, such as general fatigue, hypotonia, myalgia, and rhabdomyolysis accompanied by lack of energy. As yet, there are no preventative drugs for these VLCADD-associated metabolic attacks. Patients and methods We conducted an open-label, non-randomized, multi-center

Purpose Eating epilepsy was previously known as a kind of focal reflex epilepsy. However, the development of eating-induced multiple generalized seizures and the associated EEG changes were rarely reported. Herein, we present a 13-year-old generalized epilepsy patient with eating-induced generalized seizures since the age of 5. Case presentation The 13-year-old male patient had suffered from late-onset

Objective To assess the success rate, procedure time, and adverse events of intrathecal administration of nusinersen via the paramedian approach in adolescents and adults with spinal muscular atrophy (SMA) associated with scoliosis. Methods Seven patients with genetically confirmed SMA (age, 12–40 years) were included. Intrathecal administration of nusinersen was performed via paramedian approach using

Introduction KCNT2 was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy. Case report We present an additional observation of a 16-year-old male patient with a novel de novo KCNT2 likely pathogenic variant and review the five previously reported cases of de novo variants in this gene. Discussion Whole exome sequencing identified the missense variant c.725C > A p

Background The coexistence of falcine and occipital sinuses is rare and its natural course has not been reported. Case reports Two patients with persistent falcine and occipital sinuses are described. Both patients had straight sinuses. In one, both the transverse and sigmoid sinuses were hypoplastic and the patient had an acquired Chiari I malformation. The other patient had no other venous anomalies

Background Genetic defects in the NFU1, an iron-sulfur cluster scaffold protein coding gene, which is vital in the final stage of assembly for iron sulfur proteins, have been defined as multiple mitochondrial dysfunctions syndrome I. This disorder is a severe autosomal recessive disease with onset in early infancy. It is characterized by disruption of the energy metabolism, resulting in weakness, neurological

Introduction The ratio of cerebrospinal fluid (CSF) glucose and blood glucose is of major relevance, conducting to the diagnosis of hypoglycorrhachia, which is a sign of neuroinfection, as well as a number of neurological diseases of genetic or neoplastic etiology. Glucose in capillary sample (glucometry) is a low cost, readily available technique, as compared to venous glucose. This study aims to

Aims The current study aimed to validate the relationship between sensory characteristics and sleep dynamics among children with autism spectrum disorder (ASD) using an actigraph, which is an objective assessment device used for sleep monitoring. Methods A total of 40 children (age range, 3–6 years) participated in this study (n = 20, with ASD and n = 20, age-matched children with typical development

Biotinidase deficiency disorder is a rare inherited metabolic disorder with typical neurological manifestations of hypotonia, developmental delay, rashes, seizures, hearing and vision impairment. We present two cases with different and unusual clinical profiles, whose neuroimaging resembled Neuromyelitis Optica Spectrum Disorder. Case 1 was initially treated with immunomodulation with steroids and

Purpose To establish an objective method of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) that can assist in the diagnosis of glucose transporter 1 deficiency syndrome (GLUT1-DS). Methods FDG-PET was performed in 8 patients with a mean age of 12.5 years (range, 2–22 years) with GLUT1-DS. Their PET findings were compared with those of 45 controls with a mean age of 11.2 years (range

Background Leigh syndrome (LS) is a mitochondrial disorder that shows abnormal basal ganglia lesion and psychomotor regression. Although vitamins have been used for LS, we have not found any effective drug. Case presentation A 26-year-old man who showed psychomotor delay and short stature at the age of 1 year was diagnosed with LS according to the results of cerebrospinal fluid and high signal intensity

In lysosomal diseases, enzyme deficiency is caused by misfolding of mutant enzyme protein with abnormal steric structure that is expressed by gene mutation. Chaperone therapy is a new molecular therapeutic approach primarily for lysosomal diseases. The misfolded mutant enzyme is digested rapidly or aggregated to induce endoplasmic reticulum stress. As a result, the catalytic activity is lost. The following

Background Recent advances in respiratory management have improved survival for patients with Fukuyama congenital muscular dystrophy (FCMD), characterized by congenital muscular dystrophy and brain malformation. Previous studies reported that more than half of patients exhibit seizures in childhood. However, little is known about epilepsy after childhood. Methods To elucidate the long-term clinical

Background There is a paucity of studies on self-assessed generic health-related quality of life (HRQOL) in children with epilepsy. The purpose of this study was to investigate generic HRQOL and associated factors among Japanese children with epilepsy. Methods In this clinic-based study, 277 children (aged 8–18 years) with epilepsy and 429 children without any chronic illnesses were recruited. HRQOL

MR spectroscopy in a patient with hyponatremic encephalopathy due to the syndrome of inappropriate secretion of antidiuretic hormone revealed decreased N-acetyl-aspartate, creatine plus phosphocreatine, choline-containing compounds, and myo-inositol, with normal glutamate and increased glutamine, which normalized after Na normalization. The decreased concentrations of creatine plus phosphocreatine

Aim To evaluate the long-term effectiveness of cannabidiol (CBD)-enriched oil for the treatment of refractory epilepsy and to assess the development of tolerance to its anti-seizure effect. Methods A prospective study of 92 consecutive patients (age 1–37 years, mean-11.8 years) with treatment resistant epilepsy who were treated with cannabis oil extract (CBD/tetrahydrocannabinol [THC] ratio of 20:1)

Purpose This study aimed to analyze the topological characteristics of brain structural network in pediatric epilepsy patients with vagus nerve stimulation (VNS) by applying graph theoretical approaches. Methods Nine patients with generalized seizures and eight normal controls (NC) were enrolled. Based on diffusion tensor imaging, graph theory analysis was used to characterize the topological properties

Background The ACO2 gene encodes mitochondrial aconitase, the enzyme involved in the second step of the tricarboxylic acid cycle, catalyzing the interconversion of citrate into isocitrate. To date, fewer than 20 families harboring ACO2 mutations have been identified since the first report of a neurodegenerative disorder such as infantile cerebellar retinal degeneration in 2012. Subsequently, various

Background Agenesis of the corpus callosum (ACC) is a relatively common brain malformation in children with developmental disabilities, caused by mutations in many genes. These genetic causes are characterized by their extreme heterogeneity with more than 300 causative genes identified to date. Case report We describe two new cases from a three-generation family with ACC and a de novo mutation of the

Purpose To investigate walking ability in Japanese patients with Rett syndrome (RTT). Methods Walking ability was assessed in 100 female Japanese patients with RTT using univariate and multivariate analysis in all age groups, and in patients over 10 years of age. We analyzed walking ability and confounding factors including prenatal-perinatal histories, developmental milestones, somatic and head growth

Background Congenital Zika Virus Syndrome (CZVS) denotes the neurologic and developmental sequelae of congenital infection of the Zika virus. While prior studies have detailed the associated clinical phenotypes, new findings continue to be identified. Abnormal postures and movements have been previously described in children with CZVS, but not in detail. Objective To examine a cohort of infants with

Background A small number of studies have confirmed the presence of oxidative damage in patients with Duchenne muscular dystrophy (DMD). Nevertheless, it is unknown if there a relationship of circulating markers of oxidative stress with a muscle injury. Objective We evaluated if oxidative damage and anti-oxidant markers are associated with muscle damage in DMD. Methods This cross-sectional study included

Objectives To examine the clinical characteristics of bilirubin encephalopathy in preterm infants (pBE) in Japan. Methods We performed a two-step nationwide questionnaire survey. The initial survey determined the number of children with pBE. Using a structured questionnaire, the second survey clarified the clinical manifestations and characteristics of children with pBE, including the perinatal history

Background Generalized epilepsy and tremor phenotypes have been reported in some genetic disorders. Among them benign adult familial myoclonus epilepsy (BAFME) has been confirmed as a clearly defined clinical and genetic entity. On the other hand, non-progressive tremor and generalized epilepsy phenotypes have also been reported in patients with DHDDS variants. Case presentation. We report on a long

Background Survival of preterm very low birthweight infants resulted in high risk for developmental cognitive deficits, poor academic achievement, and behaviour disorders. While numerous studies evaluated the prevalence of neurodevelopmental disability in early childhood, poor literature is available for infants born very low birthweight in adulthood. Materials and methods Fifty-five young adults born

Introduction Epilepsy associated with tuberous sclerosis complex (TSC) has very complex clinical characteristics. Scalp electroencephalogram (EEG) fast (40–200 Hz) oscillations (FOs) were recently suggested to indicate epilepsy severity. Epileptic FOs may undergo age-dependent longitudinal change in individual patients, however, and the typical pattern of such change is not yet fully clarified. We

Background Children with epilepsy often show some degree of cognitive impairment. In this study, we investigated their learning skills to clarify the characteristics of the difficulties related to learning in Japanese-speaking children with focal epilepsy. Methods The study included 13 boys and 17 girls of mean age 9.7 years (standard deviation 2.61; range 6–14 years) with focal epilepsy and a normal

Background Children with severe motor and intellectual disabilities (SMID) are at a high risk of malnutrition and often require tube feeding to maintain their nutritional status. However, determining their energy requirements is difficult since inadequate dietary intake, severe neurological impairment, respiratory assistance, and cognitive impairment are all factors that affect malnutrition in SMID

Objectives To investigate the prevalence and background of children with medical complexity (CMC) and its secular trend in Japan. Methods CMC were defined as patients under the age of 20 years requiring medical care and devices. The patients were enrolled using the national health insurance claims data of three hospitals and two rehabilitation centers in Tottori Prefecture. The study period was divided

Aggressive immunosuppressive therapies have been proposed to treat primary angiitis of the central nervous system (PACNS). Here, we report the first successfully stabilized case of childhood, small-vessel PACNS with intravenous immunoglobulin (IVIG) therapy. A 12-year-old boy was admitted to our hospital complaining of recurrent headaches and upper-left homonymous quadrantanopia, since the age of 11 years

Background Diagnosis of functional (psychogenic) movement disorders is challenging, causing concern for many clinicians. Here, we describe a case in which MRCP (movement related cortical potentials) was useful for understanding pathophysiology. Case report The patient was a 16-year-old male with history of glycogenosis and Crohn’s disease. He also had a history of possible autism spectrum disorder

Background In the last two decades, with the advent of whole-exome and whole-genome sequencing, supplemented with linkage analysis, more than 150 genes responsible for X-linked intellectual disability have been identified. Some genes like NEXMIF remain an enigmatic entity, as often the carrier females show wide phenotypic diversity ranging from completely asymptomatic to severe intellectual disability

Tourette syndrome (TS) is a neurodevelopmental disorder defined by tics, but most patients also experience bothersome sensory phenomena, in the form of premonitory urges and/or sensory hypersensitivity. Whereas premonitory urges are temporally paired with tics, sensory hypersensitivity is a constant, heightened awareness of external and/or internal stimuli. The intensity of sensory hypersensitivity

Aim To present seven new genetically confirmed cases of biotin–thiamin-responsive basal ganglia disease (BTBGD) with different clinical and brain magnetic resonance imaging (MRI) characteristics. Material and methods Genetic variants, clinical presentations, brain MRI findings, treatment response, and prognosis of seven selected patients with BTBGD, diagnosed with SLC19A3 mutations were described.

Introduction Hypomyelinating leukodystrophies (HLDs) are genetically heterogeneous syndromes, presenting abnormalities in myelin development in the central nervous system. Recently, a recurrent de novo mutation in TMEM106B was identified to be responsible for five cases of HLD. We report the first Japanese case of TMEM106B gene mutation. Case Study A 3-year-old patient presented with nystagmus and

Background The clinical spectrum of glucose transporter type 1 deficiency syndrome (GLUT1DS) has broadened, with increasing recognition of a milder phenotype. Antibodies targeting the subunits of glutamate receptors (GluRs), including GluN1, GluN2B, and GluD2, have been detected in various neurological disorders. Anti-GluD2 antibodies in particular may be associated with cerebellar symptoms. Case report