Atypical clinical course in two patients with GNB1 variants who developed acute encephalopathy.

Introduction: Variants in the GNB1 gene, which encodes the β1 subunit of a trimeric G protein, can cause moderate to severe psychomotor retardation. Acute encephalopathies have also been observed in patients with central nervous system abnormalities; however, severe neurological sequelae have not previously been reported.

Case Presentations: Patient 1 was a Japanese female with a de novo GNB1 variant (c.

Genetic and clinical features of pediatric-onset hereditary spastic paraplegia: a single-center study in Japan.

Background And Purpose: Hereditary spastic paraplegias (HSPs) are a set of heterogeneous neurodegenerative disorders characterized by bilateral lower limb spasticity. They may present from infancy onwards at any time. Although next-generation sequencing has allowed the identification of many causative genes, little is known about which genes are specifically associated with pediatric-onset variants.

Elevation of brain gamma-aminobutyric acid levels is associated with vigabatrin-associated brain abnormalities on magnetic resonance imaging.

Objective: Vigabatrin (VGB) is an effective antiseizure medication for West syndrome. It works by irreversibly inhibiting gamma-aminobutyric acid (GABA) transaminase and increasing central GABA levels. Vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM) are an adverse effect of VGB that has only been reported in children, but the pathophysiology of this effect is unknown.

Congenital disorders of glycosylation type IIb with MOGS mutations cause early infantile epileptic encephalopathy, dysmorphic features, and hepatic dysfunction.

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.

Expanding the phenotype of COL4A1-related disorders-Four novel variants.

Objective: COL4A1 variant causes severe central nervous system (CNS) anomalies, including hydranencephaly. However, the pathogenic mechanism underlying the COL4A1 phenotype remains unclear. Here, we report de novo COL4A1 variants in four Japanese patients with typical or rare CNS involvement and exhibiting diverse phenotypes.

Autopsy Report of a Woman with Infantile Alexander Disease Who Survived 39 Years.

Patients with infantile Alexander disease (AxD) usually do not survive beyond their early teens without life support care because of progressive central hypoventilation. We present the autopsy report of a woman with infantile AxD carrying an R239C mutation in the glial fibrillary acidic protein gene, who survived 39 years. She presented with psychomotor retardation in infancy and regressed after age 5.

Epilepsy in Christianson syndrome: Two cases of Lennox-Gastaut syndrome and a review of literature.

Christianson syndrome (CS) is an X-linked intellectual disorder caused by mutations in the gene. Clinical features of CS include an inability to speak, truncal ataxia, postnatal microcephaly, hyperkinesis, and epilepsy. Almost all patients with CS develop drug-resistant epilepsy-its most serious complication.

Discordant phenotype caused by mutation in siblings with .

With the advent of next-generation sequencing (NGS), a blended phenotype has been shown to be caused by multilocus molecular diagnosis. Here, we present siblings of neurofibromatosis type 1 (NF1) with discordant phenotypes. Further genetic investigation revealed that the younger sister had trisomy 8 mosaicism with a low ratio and a known pathogenic mutation in the gene.

Long-term home non-invasive positive pressure ventilation in children: Results from a single center in Japan.

Background: Non-invasive positive pressure ventilation (NPPV) in children has recently increased worldwide and is used not only for neuromuscular diseases but for various other diseases. However, there have been few observational studies on long-term NPPV in children in Japan.

Methods: Based on medical records, we retrospectively evaluated patients aged ≤20 years who were initiated long-term NPPV at our hospital from January 2001 to December 2015.

Serial Magnetic Resonance Imaging and H-Magnetic Resonance Spectroscopy in GABA Transaminase Deficiency: A Case Report.

Gamma-aminobutyric acid transaminase (GABA-T) deficiency is a rare, autosomal recessive disorder characterized by severe psychomotor retardation, early-onset epileptic encephalopathy, intractable seizures, hypotonia, and hyperreflexia. The disease is caused by mutation in the 4-aminobutyrate aminotransferase (ABAT) gene, which encodes an enzyme involved in GABA catabolism. In this chapter, a 10-year follow-up of GABA-T deficiency in a rare case of a long-term survivor patient is discussed.

Phenotype of GABA-transaminase deficiency.

Objective: We report a case series of 10 patients with γ-aminobutyric acid (GABA)-transaminase deficiency including a novel therapeutic trial and an expanded phenotype.

Methods: Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil.

Results: All patients presented with neonatal or early infantile-onset encephalopathy; other features were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth.

Enhanced long-term potentiation in mature rats in a model of epileptic spasms with betamethasone-priming and postnatal N-methyl-D-aspartate administration.

Objective: Patients with epileptic spasms are at high risk for learning and memory impairment later in life. We examined whether synaptic plasticity is affected in the adult hippocampus, a structure responsible for learning and memory, using an animal model of epileptic spasms of unknown cause.

Methods: We produced a rat model of N-methyl-d-aspartate (NMDA)-induced spasms combined with prenatal betamethasone administration.

SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain.

Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency.

Background: Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn defect disturbing the remethylation of homocysteine to methionine (<200 reported cases). This retrospective study evaluates clinical, biochemical genetic and in vitro enzymatic data in a cohort of 33 patients.

Methods: Clinical, biochemical and treatment data was obtained from physicians by using a questionnaire.

[An 8-year-old boy with anti-NMDA receptor encephalitis, successfully treated with cyclophosphamide].

We report on an 8-year-old boy with non-paraneoplastic anti-NMDA receptor (NMDAR) encephalitis, who presented with psychotic symptoms and involuntary movement following an intractable seizure. His serum and CSF tested positive for anti-NMDAR antibodies. He received an initial immunotherapy consisting of methylprednisolone pulse therapy (mPSL) and intravenous immunoglobulin therapy (IVIg), without any clinical improvement.

[Clinical characteristics of acute encephalopathies associated with influenza H1N1-2009 in children].

We report 12 cases of acute encephalopathy associated with influenza H1N1-2009 treated according to Japanese guideline (2009). In all 12 cases, electroencephalogram presented diffuse or localized high-amplitude slow waves. Brain CT and MRI showed abnormalities in 4 and 6 cases, respectively.

Acute encephalopathy in children with Dravet syndrome.

Purpose: The occurrence of acute encephalopathy in children with Dravet syndrome has been reported sporadically. This study clarified the features of acute encephalopathy in children with Dravet syndrome.

Methods: Through the mailing list of the Annual Zao Conference on Pediatric Neurology, we collected 15 patients with clinically diagnosed Dravet syndrome, who had acute encephalopathy, defined as a condition with decreased consciousness with or without other neurologic symptoms, such as seizures, lasting for >24 h in association with infectious symptoms.

Synthesis and anti-human immunodeficiency virus activity of the skeleton isomers of 3',4'-Di-(O)-(-)-camphanoyl-(+)-khellactone.

Optically active structural isomers (1b-f and dst-1b-f) of 3',4'-di-(O)-(-)-camphanoyl-(+)-khellactone (DCK) were synthesized and their anti-human immunodeficiency virus (HIV) activity was investigated. The value of the sensitivity index (SI) of 1b was greater than that of DCK.

Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing.

Background: Conventional PCR-based direct sequencing of candidate genes for a family with X-linked leucoencephalopathy with unknown aetiology failed to identify any causative mutations.

Objective: To carry out exome sequencing of entire transcripts of the whole X chromosome to investigate a family with X linked leucoencephalopathy.

Methods And Results: Next-generation sequencing of all the transcripts of the X chromosome, after liquid-based genome partitioning, was performed on one of the two affected male subjects (the proband) and an unaffected male subject (his brother).

Paradoxical increase in seizure frequency with valproate in nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH), or glycine encephalopathy, is an autosomal recessive disorder caused by a defect in the glycine cleavage enzyme system. In neonatal-onset NKH, patients manifest lethargy, hypotonia, apnea, and intractable epileptic seizures that are not specific to this disease. We experienced a 6-year-old girl with spastic quadriplegia, intractable epilepsy, and mental retardation, all initially regarded as sequelae of neonatal meningitis.

5,10-Methylenetetrahydrofolate reductase deficiency with progressive polyneuropathy in an infant.

5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most prevalent inborn error of folate metabolism, and has variable clinical manifestations from asymptomatic to severe psychomotor retardation, microcephalus and seizure. In untreated infantile cases, it predominantly affects the central nervous system, which is sometimes fatal. On the other hand, peripheral nerve involvement is uncommon.

A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy.

Background: Deficiency of 4-aminobutyrate aminotransferase (GABA-T) is a rare disorder of GABA catabolism, with only a single sibship reported. We report on a third case, a Japanese female infant with severe psychomotor retardation and recurrent episodic lethargy with intractable seizures, with the diagnosis facilitated by proton magnetic resonance (MR) spectroscopy ((1)H-MRS).

Methods: Neuroimaging was performed at the first episode of lethargy.

[Factors associated with successful smoking cessation among adolescent smokers undergoing a smoking cessation program involving nicotine replacement therapy].

Objective: To identify factors associated with successful smoking cessation among adolescent smokers in a smoking cessation program involving nicotine replacement therapy.

Methods: We recruited adolescent smokers who were prepared to quit smoking and participated in the smoking cessation program in Kanagawa prefecture. All participants fulfilled a questionnaire beforehand, covering gender, age at the beginning of the study, age at onset of smoking, the number of quit attempts, the number of cigarettes per day and the smoking status of their families and friends.