Background Aromatic L-amino acid decarboxylase (AADC) deficiency, caused by a pathogenic variant in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disorder in which catecholamine and serotonin are not synthesized. From a large number of reports, it has been recognized that most affected patients show severe developmental delay in a bedridden state and are unable to speak. On the other

Background Ferric chelate reductase 1 like (FRRS1L) encephalopathy is a rare cause of developmental and epileptic encephalopathy. Only a few cases have been reported thus far and seizures tend to be drug refractory. We report an additional case to highlight the good seizure response to sulthiame. Case report A boy from non-consanguineous parents presented with history of ‘abnormal movements’ from 7 months

Aims To investigate the convergent validity of a new questionnaire, the Developmental Coordination Disorder Checklist (DCDC), we examined the relationship between the DCDC score and Soft Neurological Signs (SNS) which highly correlated with the Movement Assessment Battery for Children (MABC), which is widely applied to assess fine and gross motor skills. Methods The patients were 70 elementary school

Objective To describe clinical and genetic studies on a patient with early-onset spinal muscular atrophyX3 (SMAX3) with novel variant of ATP7A. Methods Clinical, neurophysiological, neuroimaging and pathological examinations were performed. Whole exome sequencing was applied to search genetic bases of this patient. Results The patient had gait abnormality from early infantile period. Muscle imaging

Introduction Autosomal dominant mitochondrial DNA depletion syndrome (MTDPS-12A) is characterized by severe hypotonia from birth due to a mutation in the adenine nucleotide translocator 1 (ANT1). Case report A 4-year-old female patient diagnosed with neonatal-onset mitochondrial disease, who had good cognitive function while receiving antiepileptic treatment, presented with sudden-onset status epilepticus

Background International reporting of epidemiological surveys of spinal muscular atrophy (SMA) in Japan has been limited to Shikoku, despite the epidemiology of the disease in countries worldwide becoming clearer. Treatments of 5q-SMA have been developed, and epidemiological studies are needed. Purpose This study aimed to conduct a nationwide epidemiological survey of SMA in Japan to clarify the actual

Objective To evaluate whether serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels predict response to adrenocorticotropic hormone (ACTH) therapy in patients with infantile spasms. Methods We prospectively evaluated patients with infantile spasms who were referred to Saitama Children’s Medical Center from January 2011 to December 2020. We measured Q-albumin

Moebius syndrome (MBS) is a congenital disorder characterized by facial and abducens palsy, sometimes accompanied with other cranial nerve palsies and comorbid conditions. Anatomical anomalies of the brainstem are assumed to be major etiologies of MBS. Its phenotypic presentation can be variable. We report a female patient with MBS who presented with neurogenic bladder (NB). She was born via normal

Objective To clarify the incidence and risk factors of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in pediatric patients with febrile status epilepticus (FSE). Methods We retrospectively surveyed patients with FSE (≥20 min and ≥40 min) who were younger than 6 years by mailing a questionnaire to 1123 hospitals in Japan. The survey period was 2 years. We then collected

Objective Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), the second most common encephalopathy syndrome in Japan, is most often associated with viral infection. Bacterial MERS has been rarely reported but is mostly associated with acute focal bacterial nephritis (AFBN) for an unknown reason. We examined cytokines and chemokines in four MERS patients with AFBN

Background Brush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain. Methods We analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter

Background Sex-determining region Y-box 2 (SOX2) plays an important role in the early embryogenesis of the eye, forebrain, and hypothalamic–pituitary axis. Anophthalmia, microphthalmia, and hormonal abnormalities are commonly observed in patients with SOX2-related disorders. Although gait disturbance, particularly ataxic gait, has recently been observed in several cases, detailed data regarding the

Background Post varicella angiopathy (PVA) is an underdiagnosed but potentially severe disease in both pediatric and adult settings. No guidelines are available for the medical and neurosurgical management of this condition. We report the first pediatric case with headache and PVA who was treated with surgical revascularization before the onset of ischemic events. Methods This case report was conducted

Background Chemotherapy in childhood leukemia potentially induces brain lesions and neurological sequelae. Paroxysmal sympathetic hyperactivity (PSH) is known as a treatment-associated complication; however, the full clinical spectra of PSH remain to be elusive. Case report A 5-year-old girl was diagnosed of acute myeloid leukemia (AML) M5. After the intensification therapy, she developed recurrent

Background The collagen type IV alpha 1 chain (COL4A1) gene on 13q34 encodes one chain of collagen. COL4A1 mutations have been identified as the cause of a group of multisystemic conditions in humans, including the brain, eyes, kidneys, muscles, and other organs at any age. Brain imaging shows a wide spectrum of abnormalities, including porencephaly, schizencephaly, polymicrogyria focal cortical dysplasia

Background Neurodegeneration with brain iron accumulation (NBIA) is a group of rare inherited neurodegenerative disorders. Ten types of NBIA are known. Studies reporting various NBIA subtypes together are few. This study was aimed at describing clinical features, neuroimaging findings, and genetic mutations of different NBIA group disorders. Methods Clinical, radiological, and genetic data of patients

Herpes simplex encephalitis is the most common cause of sporadic fatal encephalitis. More than half of patients with herpes simplex encephalitis will die and the vast majority of survivors have severe neurologic sequelae without effective antiviral therapy. Some people experience relapses such as secondary anti-N-methyl-d-aspartate receptor encephalitis despite appropriate antiviral treatment. It is

Introduction Recently, many seriously ill children requiring medical equipment are being recommended to transition from hospital to home care in Japan. Since 2011, our recovery center has provided a support program for the transfer process from hospital to home for ill children and their families. The purpose of this study was to evaluate the factors related to high care burden after completing the

Background The clinical severity of Sandhoff disease is known to vary widely. Furthermore, long-term follow-up report is very limited in the literature. Case presentation We present a long-term follow-up report of a patient with juvenile-onset Sandhoff disease with a motor neuron disease phenotype. The patient had compound heterozygous variants of HEXB (p.Trp460Arg, p. Arg533His); the Trp460Arg was

In recent years, with advances in molecular genetics, many new mutations with various ataxic syndromes have been identified. Recently, homozygous sequestosome 1 (SQSTM1) gene variant with a progressive childhood-onset cerebellar ataxia, dystonia and gaze palsy was described. Here we describe a patient with progressive cerebellar ataxia and gaze palsy, as well as myoclonus, cognitive impairment and

Background Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous deletion or intragenic mutation of the SMN1 gene. It is well-known that high copy number of its homologous gene, SMN2, modifies the phenotype of SMN1-deleted patients. However, in the patients with intragenic SMN1 mutation, the relationship between phenotype and SMN2 copy number remains unclear

Objective Autosomal dominant (AD) guanosine triphosphate cyclohydrolase 1 (GCH1) deficiency is the most common cause of dopa-responsive dystonia (DRD). Patients with GCH1 deficiency are likely to experience diagnostic delay, but its consequences have not been described thoroughly in patients with early-onset disease. We describe the diagnostic delay and residual motor signs (RMS) observed in patients

Aim To elucidate the morphological characteristics of spike-wave complexes (SWCs) causing myoclonic seizures (MS) in childhood-onset idiopathic myoclonic epilepsies. Subjects and Methods The subjects were 8 patients, including 4 with epilepsy with myoclonic-atonic seizures (EMAS), 3 with myoclonic epilepsy in infancy (MEI) and 1 with idiopathic unclassifiable myoclonic epilepsy. Morphometric parameters

Background DYT-TOR1A is caused by a GAG deletion in the TOR1A gene. While it usually manifests as early-onset dystonia, its phenotype is extremely diverse, even within one family. Recent reports have revealed that some DYT-TOR1A cases have novel mutations in the TOR1A gene while others have mutations in both TOR1A and another DYT gene (THAP1 or SGCE). Our understanding of the correlation between genotype

Variants in the myogenesis-regulating glycosidase (MYORG) gene which is known as the first autosomal recessive gene that has been associated with primary familial brain calcification (AR-PFBC). Although adult patients have been reported, no pediatric case has been reported until now. Herein, we review the clinical and radiological features of all AR- PFBC patients with biallelic variants in the MYORG

Background Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a hereditary disorder caused by biallelic variants in the EARS2 gene. Patients exhibit developmental delay, hypotonia, and hyperreflexia. Brain magnetic resonance imaging (MRI) reveals T2-hyperintensities in the deep white matter, thalamus, and brainstem, which generally stabilize over time. Herein, we

Background Transient periictal MRI abnormalities (TPMA) are caused by seizures, and may completely or partially reverse within a few days following seizure. Although TPMA are usually observed in patients with status epilepticus (SE), they have also been rarely reported after isolated/recurrent seizures not fulfilling the criteria for SE. Herein, we present a case of a 1-year-old girl with TPMA. Case

Background Severe loss of TBCE function has been related to two well-known dysmorphic syndromes, while TBCE hypomorphic variants have been linked to neurodegenerative conditions due to perturbed microtubule dynamics and homeostasis, with signs of central and peripheral nervous system involvement. Method We report on an Italian female originating from Southern Italy who presented early-onset regression

Objectives Cytotoxic lesions of the corpus callosum (CLOCCs) are secondary lesions associated with entities like infection manifested by restricted diffusion on diffusion-weighted cranial magnetic resonance imaging. Our objectives are to evaluate the clinic-radiological spectrum of pediatric patients with cytotoxic lesions of the corpus callosum (CC). Methods Children (0–18 years) admitted between

Objective To evaluate the clinical utility of next-generation sequencing (NGS) in unexplained pediatric epilepsy, and to identify the potential predictors associated with Mendelian genetic causes. Methods Two hundred and ten children with unexplained epilepsy, who underwent NGS test were included. We analyzed the demographic, clinical and genetic characteristics, and executed a Logistic regression

Background PURA-related neurodevelopmental disorders (PURA-NDDs) include 5q31.3 deletion syndrome and PURA syndrome. PURA-NDDs are characterized by neonatal hypotonia, moderate to severe global developmental delay/intellectual disability (GDD/ID), facial dysmorphism, epileptic seizures, nonepileptic movement disorders, and ophthalmological problems. PURA-NDDs have recently been identified and underestimated

Background ALG12-CDG is a rare autosomal recessive type I congenital disorder of glycosylation (CDG) due to pathogenic variants in ALG12 which encodes the dolichyl-P-mannose:Man-7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase. Thirteen patients from unrelated 11 families have been reported, most of them result in broad multisystem manifestations with clinical variability. It is important to validate

Background Familial hemiplegic migraine (FHM) is an inherited autosomal dominant disorder characterized by migraine with reversible hemiplegia. FHM1 is caused by variants in CACNA1A, encoding a P/Q type neuronal voltage-gated calcium channel α subunit, which is also associated with episodic ataxia type 2 (EA2). FHM2 is associated with ATP1A2, which codes for an Na+/K+-ATPase isoform 2 subunit. Case

Background Autoimmune mediated encephalitis (AME), which includes autoantibody-associated encephalitis and acute disseminated encephalomyelitis, is a common cause of encephalitis as well as infectious encephalitis in children. AME may be triggered by autoimmune responses to paraneoplastic syndromes and infections. Infectious encephalitis associated with an immunocompromised status caused by anti-cancer

Background The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot–Marie–Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who

Background Joubert syndrome is an autosomal recessive or X-linked genetic disease with a cerebellar vermis defect or hypoplasia, hypotonia, ocular dyskinesia, and mental retardation. In neonates, respiratory problems such as apnea and tachypnea are notable. Case report We report a patient Joubert syndrome with a homozygous NPHP1 variant, who had head titubation with irritability, including exaggerated

Background Memantine is an N-methyl-D-aspartate receptor (NMDA-R) antagonist, approved for dementia, but also studied in pediatric autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Methods We reviewed children treated with memantine in a single-centre pediatric neurology clinic. Clinical data extracted included age, sex, weight, clinical history, reason for memantine

Background Nonconvulsive status epilepticus (NCSE) comprises a range of conditions in which prolonged electrographic seizures result in nonconvulsive clinical symptoms. An understanding of NCSE is especially important in emergency care. Among the various causes of NCSE, an infectious etiology has been rarely reported to date. Case reports We report two pediatric cases of rotavirus gastroenteritis complicated

Background Acute necrotizing encephalopathy (ANE) is a severe encephalopathy associated with acute viral infection. While most ANE cases are sporadic, pathogenic variants in the gene RAN binding protein 2 (RANBP2) have been identified as a major cause of familial or recurrent ANE (ANE1). Although sporadic ANE predominantly affects Asian children, ANE1 is very rare in east Asia. Case report A 1-year-7-month-old

Background Primary angiitis of the central nervous system (PACNS) is a newly-emerging disease, and it is known that early diagnosis with treatment is important for the improvement of prognosis. Case description Here, we report the case of a previously healthy 13-year-old girl who presented with right eye abduction failure, attributed to isolated right sixth nerve palsy, as the initial symptom of PACNS

Purpose Forced normalization (FN) indicates psychotic episodes associated with seizure remission and disappearance of epileptiform activity on EEG. FN is likely to occur when frequent seizures are abruptly terminated by anti-epileptic drugs (AEDs) or epilepsy surgery. Methods We describe an atypical case of a patient with FN induced by lacosamide (LCM). Results A 23-year-old female patient with Lennox-Gastaut

Objective Physiological gamma and ripple activities may be linked to neurocognitive functions. This study investigated the relationship between development and non-epileptic, probably physiological, fast (40–200 Hz) oscillations (FOs) including gamma (40 – 80 Hz) and ripple (80 – 200 Hz) oscillations in scalp EEG in children with neurodevelopmental disorders. Methods Participants were 124 children

Background Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a progressive neurodegenerative disorder with stroke-like lesions. The common MRI findings are gyral swelling and high signal intensity on T2WI/FLAIR images crossing the vascular territories. We have observed a linear cystic lesion and a laminar necrosis in the affected cortices of MELAS patients

Background Dyslexia is a neurodevelopmental disorder which occurs in childhood but continues to influence academic and occupational function in adulthood. Recently, a Japanese dyslexia questionnaire and diagnostic procedure was established for primary school children. However, there is currently no procedure for the diagnosis or screening of dyslexia in individuals at or above junior high school age;

The purpose of this study is to investigate the effects of a program containing a combination of social skills training (SST) and parenting training (PT) for the enrichment of social interaction skills and reduction of parenting stress for children with high-functioning autism spectrum disorder (HFASD) and their parents in Japan. Twenty-two patients with HFASD from second to fourth grade and their

Background FGF12 (FHF1) gene encodes voltage-gated sodium channel (Nav)-binding protein fibroblast growth factor homologous factor 1, which could cause seizures by regulating voltage dependence of Nav fast inactivation and neuron excitability. The most common pathogenic variant FGF12 c.341G > A related early-onset epileptic encephalopathies (EOEE) was characterized by intractable seizures and developmental

Objective The aim of this study was to assess the risk of recurrence after a first unprovoked seizure in childhood and to explore the correlation between the first and second seizures in recurrent patients. Methods In a prospective study, we included 467 children aged 1 month to 16 years, who were attended to between November 1, 2008 and October 31, 2016 following a first seizure. Children who had

Background Heterozygous mutations in the PACS1 gene have been shown to cause Schuurs-Hoeijmakers syndrome, a rare condition characterized by intellectual disability and peculiar facial dysmorphisms. To date, 52 cases have been reported (49 postnatally and 3 prenatally diagnosed). Case report: We describe a child carrying the recurrent PACS1 c.607C>A variant; besides the typical neurodevelopmental and

Objective This study aimed to investigate the associations between psychopathological characteristics of children and adolescents with primary headache, as measured by the Strengths and Difficulties Questionnaire (SDQ), and treatment outcomes. Methods A cohort study was conducted on 124 pediatric patients with primary headache. At the first consultation, the SDQ was completed by the parents. The analysis

Background The most common causative pathogen of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was reported as HHV-6. Although excitotoxic injury with delayed neuronal death is considered to be a possible pathogenesis of AESD, the detailed pathophysiology remains unclear. Case presentation We present a twelve-month-old girl with AESD due to HHV-6 primary infection. She

In mucopolysaccharidoses (MPS), spinal cord compression (SCC) resulting from glycosaminoglycan (GAG) accumulation is a critical complication that can cause significant neurological and respiratory morbidities. However, clinically similar disorders such as mucolipidosis types II and III (ML) with SCC have been scarcely reported. Herein, we report four patients with ML who had SCC. Brain MRI revealed

Objective We aimed to assess the efficacy and safety of high-dose pyridoxine treatment for seizures and its effects on development in patients with inherited glycosylphosphatidylinositol deficiencies (IGDs). Methods In this prospective open-label multicenter pilot study, we enrolled patients diagnosed with IGDs using flow cytometry and/or genetic tests. The patients received oral pyridoxine (20–30 mg/kg/day)

Objective Our goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases. Methods We retrospectively studied

Objective Reversible splenium lesions during febrile illness (RESLEF) are found in a spectrum. There are two types of corpus callosum (CC) lesions: CC-only type, with limited lesions and the CC (+) type, with extensive white-matter lesions. This retrospective study aimed to describe the differences in clinical findings between CC-only and CC (+) lesions and the association between onset age and clinico-radiological

Objective To elucidate the clinical characteristics of Japanese pediatric patients with acquired demyelinating diseases (ADS), positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG), we conducted a nation-wide survey. Methods Information about pediatric patients under 18 years old with ADS was solicited with surveys sent to 323 facilities. In an initial survey, we asked whether the center

Background Arterial spin labeling, a magnetic resonance imaging modality that can evaluate cerebral perfusion without using a contrast material or ionizing radiation, is becoming increasingly accessible. However, only a few reports have used this method to assess the perfusion abnormalities observed in acute encephalopathy with biphasic seizures and late reduced diffusion. Patient description A 10-month-old

Background The MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish

Guillain-Barré syndrome (GBS) is the most prevalent cause of acquired paralytic neuropathy in children, however, ataxia as the initial presenting sign in children is very rare. Antiganglioside antibodies are presumed to have an important role in the pathophysiology and some phenotypic correlations have been reported. Anti-GM2 antibody, unlike other antibodies, is far less detected in GBS. Here, we

Introduction This study describes the specific neuropsychological abnormalities among children with epilepsy (CH-E) living in Georgia. Methods A cohort of CH-E and children without epilepsy (CH-NoE), aged 6–13 years, admitted to the epilepsy center of the Institute of Neurology and Neuropsychology from 1st January 2010 to 31st December 2015, was selected and investigated with a structured protocol

Introduction SCN8A-related epilepsy has various phenotypes. In particular, patients with developmental and epileptic encephalopathy (DEE) are resistant to antiepileptic drugs and may present with autonomic symptoms, such as marked bradycardia and apnea during seizures, and thus have an increased risk of sudden death. Herein, we report a case of very severe SCN8A-related epilepsy necessitating cardiac