Objective It may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM. Methods This prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5–16.2) with a first episode of ATM. Factors associated with

Two brothers with an IQSEC2 pathogenic variant presented with early onset intellectual disability, intractable epileptic seizures, autism spectrum disorders, postnatal microcephalus and slowly progressive rigid-spasticity. Their epileptic seizures were characterized by intractability, early onset epileptic spasms, and then clusters of tonic/tonic-clonic seizures, exacerbated by valproate. Electroencephalography

Background Pathogenic variants in the dynamin 1 like gene are related to abnormal mitochondrial dynamics and distributions and are associated to variable clinical phenotypes. A few patients harboring the p.Arg403Cys missense variant appears to be different from the classical, more severe phenotypes, showing sudden onset of drug resistant seizures after a previously normal or slightly delayed development

Background Epilepsy is known to be associated with Tay-Sachs disease (TSD); however, no detailed reports are available. This case report aimed to present the clinical features of late onset spasms (LOS) in a patient with infantile TSD, and to elucidate the pathophysiology leading to LOS, using proton magnetic resonance spectroscopy (MRS). Case presentation At 11 months old, our patient had an afebrile

Background Attention-deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorders among school-age children worldwide. In a more recent follow-up study, Biederman et al. found that 78% of children diagnosed with ADHD between the ages of 6–17 years continued to have a full (35%) or a partial persistence after eleven years. Objective In this study, it was aimed to identify the

The objective of this study was to identify developmental trajectories of developmental/behavioral phenotypes and possibly their relationship to epilepsy and genotype by analyzing developmental and behavioral features collected prospectively and longitudinally in a cohort of patients with Dravet syndrome (DS). Thirty-four patients from seven Italian tertiary pediatric neurology centers were enrolled

Background Epilepsy with myoclonic absences (EMA) is a rare childhood-onset syndrome characterized by absences of responsiveness accompanied by bilateral rhythmic clonic-like myoclonic jerks. Herein, we describe the case of a child with EMA, resistant to multiple commonly used antiepileptic drugs, in whom low-dose phenobarbital unexpectedly achieved complete remission of epilepsy. Case report A 10-year-old

Background Rapid-onset dystonia–parkinsonism (RDP) is a disease characterized by an abrupt onset of dystonia accompanied by signs of parkinsonism and prominent bulbar symptoms. Case report We describe a case of a female patient, born after normal delivery, but diagnosed with mild intellectual disability at age 7. She presented with an abrupt onset of upper limb dystonia and bradykinesia without tremor

Background Increasing clinical and scientific attention is given to the transition of neurological stages from child to adult. Data on brain plasticity during adolescence is interesting for providing adequate evidence-based medical attention to neurological conditions in this population. Acquired aphasia is well described in adults and children, but not in adolescence. Objective We describe a 5-year

Objective Patients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments. Methods We recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients

Objective The current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E). Methods This is a retrospective study on patients

Objectives We aimed to determine serum 25-hydroxyvitamin D (25(OH)D) and undercarboxylated osteocalcin (ucOC) levels in severe motor and intellectual disabilities (SMID) patients and their association with bone turnover biomarkers. Methods We assessed vitamin D and K levels as indicators of osteoporosis in institutionalized adults with SMID. From December 2019 to February 2020, 93 institutionalized

Background ECHS1 is a key enzyme of the valine catabolic pathway and oxidation of fatty acids. In ECHS1 deficiency (ECHS1D), accumulation of toxic intermediates from the valine induces neurodegeneration, which presents Leigh syndrome (LS). Therefore, valine restriction is suggested as an effective therapy. Further, cysteamine may detoxify the toxic metabolites themselves and N-acetylcysteine (NAC)

Background Aicardi-Goutières syndrome (AGS) is a clinically and genetically heterogenous autoinflammatory disorder caused by constitutive activation of the type I interferon axis. It has been associated with the genes TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, IFIH1. The clinical diagnosis of AGS is usually made in the context of early-onset encephalopathy in combination with basal ganglia

Background Recent studies have suggested that two PACS2 pathogenic variants, c.625G > A (p.Glu209Lys) and c.631G > A (p.Glu211Lys), have been causally linked to the characteristic developmental and epileptic encephalopathy, including autistic behaviors, hypotonia, cerebellar dysgenesis and facial dysmorphism. Their seizures appear most difficult to control in neonatal and infant period, but improve

Objective Describe the outcome of a Malaysian cohort of children with acute necrotising encephalopathy (ANE). Method Retrospective study of children with ANE seen at University of Malaya Medical Centre from 2014 to 2019. All clinical details including ANE-severity score (ANE-SS), immunomodulation treatment and neurodevelopmental long-term outcome were collected. Results Thirteen patients had ANE and

Introduction Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are neurodevelopmental disorders caused by loss of function of maternally expressed UBE3A and paternally expressed contiguous genes on chromosome 15q11-13, respectively. A majority of these syndromes suffer from a large deletion of the relevant chromosome (AS Del or PWS Del), which includes biallelically expressed gamma-aminobutyric

Background Incontinentia pigmenti (IP) is an X-linked neurocutaneous disorder that can present with cerebral arteriopathy during early infancy. However, no previous reports have demonstrated arteriopathic manifestations during postinfantile childhood in patients with IP. Patient description We describe a case of IP in a 2-year-old girl who developed encephalopathic manifestations associated with influenza

Background Reversible lesions in the splenium of the corpus callosum (SCC) with viral infections are associated mainly with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We report a pediatric patient in thyroid crisis with reversible SCC lesions. Case description We diagnosed a 9-year-old girl with thyroid crisis. She had presented with fever, tachycardia, and

Introduction Epilepsy is one of the main clinical problems in Angelman syndrome (AS). Seizures typically start in early childhood then decrease or are often alleviated by young adulthood. Several studies using AS model mice showed comparable seizure susceptibility during young adulthood. In contrast, the course of epilepsy post young adulthood differs from persistently relieved to rerising among reports

Introduction Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their correct tRNAs. Bi-allelic truncating variants in the AIMP1 gene have been associated with hypomyelinating leukodystrophy-3 (HLD3; MIM 260600), which is characterized by hypomyelination, microcephaly

Background Chromodomain helicase DNA-binding (CHD) proteins play important roles in developmental processes. CHD3, a member of the CHD family of proteins, was reported to be a cause of a neurodevelopmental syndrome by Snijders Blok et al., but only a small number of probands have been reported. Case report The patient was a 9-year-old female with severe intellectual disability, speech impairment, autism

Background Status dystonicus is an underdiagnosed condition, probably due to heterogeneous etiology, presentation and course. Herein, we report the first case of CLN8 disease in the literature presenting with status dystonicus who responded well to pharmacological intervention. Case A boy aged five years and three months presented with fever, loss of appetite, intermittent excessive dystonic contractions

Background Mutations in GNAO1 typically result in neurodevelopmental disorders, including involuntary movements. They may be improved using calcium-channel modulators. Case The patient visited our hospital at age 2 years because of moderate global developmental delay. Her intermittent, generalized involuntary movements started at age 8 years. A de novo GNAO1 mutation, NM_020988.2:c.626G > A, (p.Arg209Cys)

Introduction Children with either febrile seizure or acute encephalopathy exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF). Among children with SICF, we previously reported those who have refractory status epilepticus or prolonged neurological abnormalities with normal AST levels are at a high risk for the development of acute encephalopathy with biphasic

Introductions A specific mutation in the ACTA2 gene is known to cause multisystemic smooth muscle dysfunction syndrome, which is associated with cerebrovascular diseases and various organ disorders. Cerebral infarctions resulting from severe vasculopathy can be refractory; however, there are no previous reports describing the detailed clinical course of recurrent cerebral infarctions due to an ACTA2

Objective The World Health Organization International Classification of Functioning, Disability and Health Framework (ICF) states that a child’s health conditions, functions, activities, participation in life and contextual factors shape disability. Research on the development of children with organic acidemias (OA) mostly focused on cognitive and medical outcomes. This study aimed to examine adaptive

Background Childhood cerebral adrenoleukodystrophy (CCALD) is the most common phenotype of adrenoleukodystrophy (ALD) and is characterized by the progression of intellectual, psychic, visual, and gait disturbances. Progression of this intractable disease can only be prevented by hematopoietic stem cell transplantation during the early stages of the disease. The aim of this study was to clinically evaluate

Background Perampanel is the latest anti-seizure medication introduced in the Philippines in 2015. This was initially approved as an adjunctive treatment for focal seizures and those with secondary generalization among individuals 12 years old and above. By March 2020, it has been approved also for generalized seizures and in children 4 years and above. The general objective of this research is to

Background Marked decreases in serum creatine kinase levels have been noted in Duchenne and Becker muscular dystrophies as rare complications of autoimmune or autoinflammatory diseases. Subjects and methods The influence of systemic inflammation on serum creatine kinase levels was reviewed from the charts of three subjects with Fukuyama congenital muscular dystrophy. Results A total of 30 infectious

Spinocerebellar ataxia, autosomal recessive 2 (SCAR2) [MIM:213200] is a rare autosomal recessive disease of spinocerebellar ataxia associated with degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. Recently, several PMPCA gene variants have been reported in SCAR2

Background MICPCH is manifested as microcephaly associated with pontocerebellar hypoplasia and global developmental delay but developmental regression has never been reported. We describe the detailed clinical history of a woman with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH) with a CASK mutation who exhibited gross motor regression after adolescence. Case:

Background Children with refractory epilepsy (RE) are associated with increased mortality rate, nonfatal injuries, disability, and diminished quality of life. Biomarkers for the early prediction of RE is still an unmet need. Methods Eighteen children with RE and six age-matched unrelated controls were included in this study. Plasma samples were prefractionated by the optimized thermal treatment before

Aim MOGS mutations cause congenital disorders of glycosylation type IIb (CDG-IIb or GCS1-CDG). The specific manifestations caused by the mutations in this gene remain unknown. We aimed to describe the clinical features of CDG- IIb and the effectiveness of urinary oligosaccharide analysis in the diagnosis of CDG- IIb. Methods Patient 1 was analyzed with whole-exome sequencing (WES) to identify the causative

Background CHOPS syndrome, caused by a mutation in the AFF4 gene, is a recently established and extremely rare genetic disorder, which has moderate phenotypic overlap with Cornelia de Lange syndrome. The main phenotypes include characteristic facial features, short stature, obesity, skeletal and pulmonary involvement, and neurodevelopmental impairment. Case report We report on a Korean girl with CHOPS

Paroxysmal abnormal eye movement in early infancy is one of the initial symptoms of glucose transporter 1 deficiency syndrome (GLUT1DS). We describe four early infants with transient hypoglycorrhachia presenting with abnormal eye movements. Their symptoms disappeared after the introduction of a ketogenic diet (KD), and their development was normal. Since no variants in SLC2A1 were detected, the CSF-to-blood

Aim To explore the relationships between transient structural brain patterns on MRI at preterm and at term-equivalent age (TEA) as a predictor of general movements (GMs) and motor development at 1-year corrected age (CA) in very preterm infants. Methods In this prospective study, 30 very preterm infants (median = 28wks; 16 males) had structural magnetic resonance imaging (MRI) at preterm (median = 31wks + 6d)

Peroxisomal acyl-CoA oxidase (ACOX1) deficiency is a rare autosomal recessive single enzyme deficiency characterized by hypotonia, seizures, failure to thrive, developmental delay, and neurological regression starting from approximately 3 years of age. Here, we report two siblings with ACOX1 deficiency born to non-consanguineous Japanese parents. They showed mild global developmental delay from infancy

Background Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay, hypotonia and seizures. Results We report a patient with PKS showing unique polymicrogyria with calcification. He had delayed development and dysmorphic facial features including frontal bossing, hypertelorism, and high arched

Background The periodic paralyses are a group of skeletal muscle channelopathies caused by variants in several ion channel genes. Potassium Inwardly Rectifying Channel Subfamily J Member 5 (KCNJ5) encodes the G-protein–activated inwardly rectifying potassium channel 4 (Kir3.4) and the heterozygous KCNJ5 variants cause familial hyperaldosteronism and long QT syndrome (LQTS). Recent studies suggested

Background In approximately half of patients with epilepsy and intellectual disability (ID), the cause is unidentified and could be a mutation in a new disease gene. Patient description To determine the discovery of disease-causing mutation in a female patient with epilepsy and ID, we performed trio whole-exome sequencing, reverse transcription polymerase chain reaction (RT-PCR) followed by Sanger

Introduction Dravet syndrome (DS) is severe myoclonic epilepsy in infancy and associated with a heterozygous mutation of the gene for the sodium channel alpha 1 subunit (SCN1A). Recently, adult patients with DS have been reported to show parkinsonism, but no corresponding neuroimaging data are available. Here, we present neuroimaging data in 2 adult patients with DS showing parkinsonian symptoms. Case

Background Walker-Warburg syndrome (WWS), an autosomal recessive disease, is the most severe phenotype of congenital muscular dystrophies. Its diagnosis remains primarily clinical and radiological. Identification of its causative variants will assist genetic counseling. We aim to describe genetic and neuroimaging findings of WWS and investigate the correlation between them. Methods We retrospectively

Background Symptoms and findings called orange or red flags may indicate the etiology of pediatric headaches and may point to a life-threatening situation requiring urgent treatment and thus can alter patient management. These findings can be either misleading or prognostic for clinicians. We aimed to identify the etiology and prognostic value of orange/red flags in pediatric patients. Methods This

Background Mutations in the XPR1 gene are associated with primary familial brain calcifications (PFBC). All reported mutations are missense and inherited as an autosomal dominant trait. PFBC patients exhibited movement disorders, neuropsychiatric symptoms, and other associated symptoms with diverse severity, even within the same family. Materials and methods We identified and enrolled a patient with

Background CUL3 encodes cullin-3, a core component of a ubiquitin E3 ligase. CUL3 mutations have recently been associated with autism spectrum disorder (ASD); however, the detailed clinical courses have been described in only a limited number of patients with CUL3 mutations and neurodevelopmental diseases, including ASD. Case report A 21-month-old Japanese girl presented with febrile status epilepticus

Background Peripheral nerve imaging is increasingly recognized as a powerful tool to evaluate nerve hypertrophy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Charcot-Marie-Tooth diseases (CMT), whereas data in pediatric patients are limited. Case description We describe the case of a 15-year-old Japanese girl with asymmetric demyelinating polyneuropathy, who, at the age of

Background Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) is an extremely rare autosomal recessive disorder with variable expressivity, caused by biallelic mutations in the PTRH2 gene. Core features are global developmental delay or isolated speech delay, intellectual disability, sensorineural hearing loss, ataxia, and pancreatic insufficiency (both exocrine and

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