Correlation of augmented startle reflex with brainstem electrophysiological responses in Tay-Sachs disease.

Aim: To clarify the evolution of an augmented startle reflex in Tay-Sachs disease and compare the temporal relationship between this reflex and brainstem evoked potentials.

Subjects And Methods: Clinical and electrophysiological data from 3 patients with Tay-Sachs disease were retrospectively collected.

Results: The augmented startle reflex appeared between the age of 3 and 17 months and disappeared between the age of 4 and 6 years.

Attenuation of endoplasmic reticulum stress in Pelizaeus-Merzbacher disease by an anti-malaria drug, chloroquine.

Pelizaeus-Merzbacher disease (PMD) is a hypomyelinating disorder caused by the duplication and missense mutations of the proteolipid protein 1 (PLP1) gene. PLP1 missense proteins accumulate in the endoplasmic reticulum (ER) of premature oligodendrocytes and induce severe ER stress followed by apoptosis of the cells. Here, we demonstrate that an anti-malaria drug, chloroquine, decreases the amount of an ER-resident mutant PLP1 containing an alanine-243 to valine (A243V) substitution, which induces severe PMD in human.

Hypophosphatemia is a common complication in severely disabled individuals with neurological disorders and is caused by infection, refeeding and Fanconi syndrome.

Aim: To describe the characteristics of hypophosphatemia in severely disabled individuals with neurological disorders and to identify its causative factors.

Method: We retrospectively reviewed clinical data from 82 individuals with motor skills classified as sitting, rollover or bedridden. Age, gender and body mass index were compared in individuals with (n=19) and without (n=63) a history of hypophosphatemia (serum phosphate levels <2.

Plasmablasts as migratory IgG-producing cells in the pathogenesis of neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory disease characterized by recurrent attacks of optic neuritis and myelitis. It is generally accepted that autoantibodies against aquaporin 4 water channel protein play a pathogenic role in neuromyelitis optica. We have recently reported that plasmablasts are increased in the peripheral blood of this autoimmune disease, and are capable of producing autoantibodies against aquaporin 4.

[Pathogenesis of inclusion body myositis: autoimmune or degenerative disease?].

While the pathogenesis of inclusion body myositis (IBM) remains undetermined, there are two major hypotheses: the autoimmune hypothesis and the degeneration hypothesis. Herein, we review these hypotheses as well as potential therapeutic approaches. Evidence in favor of a primary autoimmune etiology includes the frequent complication of other autoimmune diseases in patients with IBM and the presence of autoantibodies against cytosolic 5'-nucleotidase 1A.

Long-term developmental outcome after early hemispherotomy for hemimegalencephaly in infants with epileptic encephalopathy.

This study aimed to identify the effect of early hemispherotomy on development in a consecutive series of 12 infants with hemimegalencephaly (HME) demonstrating epileptic encephalopathy. Mean age at onset was 20.4 days (range, 1-140), mean age at surgery was 4.

Highly efficient in vivo delivery of PMO into regenerating myotubes and rescue in laminin-α2 chain-null congenital muscular dystrophy mice.

Phosphorodiamidate morpholino oligomer (PMO)-mediated exon skipping is among the more promising approaches to the treatment of several neuromuscular disorders including Duchenne muscular dystrophy. The main weakness of this approach arises from the low efficiency and sporadic nature of the delivery of charge-neutral PMO into muscle fibers, the mechanism of which is unknown. In this study, to test our hypothesis that muscle fibers take up PMO more efficiently during myotube formation, we induced synchronous muscle regeneration by injection of cardiotoxin into the tibialis anterior muscle of Dmd exon 52-deficient mdx52 and wild-type mice.

Depletion of molecular chaperones from the endoplasmic reticulum and fragmentation of the Golgi apparatus associated with pathogenesis in Pelizaeus-Merzbacher disease.

Missense mutations in the proteolipid protein 1 (PLP1) gene cause a wide spectrum of hypomyelinating disorders, from mild spastic paraplegia type 2 to severe Pelizaeus-Merzbacher disease (PMD). Mutant PLP1 accumulates in the endoplasmic reticulum (ER) and induces ER stress. However, the link between the clinical severity of PMD and the cellular response induced by mutant PLP1 remains largely unknown.

Hypoalbuminemia in early onset dentatorubral-pallidoluysian atrophy due to leakage of albumin in multiple organs.

We delineate a complication of hypoalbuminemia in dentatorubral-pallidoluysian atrophy (DRPLA), which we have found to be common in this disorder. In addition, we explored the pathogenesis of this phenomenon through clinical and histological examinations. Clinical course and laboratory findings of nine patients with childhood-onset DRPLA (aged 6-49 years; CAG repeat length 62-93) were retrospectively reviewed.

[Sialic acid supplementation therapy for distal myopathy with rimmed vacuoles (GNE myopathy)].

Distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy, for which new nomenclature "GNE myopathy" is now proposed, is an autosomal recessive disease that preferentially affects tibialis anterior and hamstrings muscles in young adults. The disease is caused by mutations, mostly missense, in GNE gene that encodes a protein with two enzymatic activities in sialic acid biosynthetic pathway: UDP-GlcNAc 2-epimerase and ManNAc kinase. Accordingly, sialic acid production is reduced in patients' cells and cells are hyposialylated.

[Recent advances in facioscapulohumeral muscular dystrophy].

Facioscapulohumeral muscular dystrophy (FSHD) is a common autosomal dominant muscular dystrophy caused by truncation of D4Z4 repeat array on chromosome 4q35. Facial and shoulder-girdle muscles are preferentially affected but clinical symptoms are quite variable even within the same family. Asymmetrical muscle involvement is also characteristic in this disease.

Brain-derived neurotrophic factor and glucocorticoids: reciprocal influence on the central nervous system.

Brain-derived neurotrophic factor (BDNF) has multiple roles in the central nervous system (CNS), including maintaining cell survival and regulation of synaptic function. In CNS neurons, BDNF triggers activation of phospholipase Cγ (PLCγ), mitogen-activated protein/extracellular signal-regulated kinase (MAPK/ERK), and phosphoinositide 3-kinase (PI3K)/Akt pathways, influencing neuronal cells beneficially through these intracellular signaling cascades. There is evidence to suggest that decreased BDNF expression or function is related to the pathophysiology of brain diseases including psychiatric disorders.

[Effects of a rich emotionally-satisfying childbirth experience of mothers on their later parental attitudes and behavior in school-age children].

This study examined the effects of a rich, emotionally-satisfying childbirth experience (CBE) of mothers on the behavior of school-age children using longitudinal data measured from immediately to 7 years and 6 months after birth. The results of structural equation modeling revealed the following: 1) giving birth in a midwifery center enhances emotional satisfaction with CBE, 2) a rich CBE of mothers was associated with parental warmth, 3) parental warmth during early childhood increased prosocial behavior and reduced behavioral problems in school-age children, and 4) temperamentally difficulty in early childhood were linked to later behavioral problems in school-age children. Thus, a rich CBE and parental warmth were suggested to be factors contributing to the good behavior of school-age children.

Malformations of cortical development with good clinical outcome: a case report and review of literature.

Malformations of cortical development (MCD) are important causes of chronic epilepsy. MCD encompass many varied disorders with diverse clinical manifestations. Schizencephaly, one of the MCD, is known to be complicated by various types of epilepsy, most of which are intractable.

High gamma activity of 60-70 Hz in the area surrounding a cortical tuber in an infant with tuberous sclerosis.

Purpose: To detect the epileptogenic region causing epileptic spasms in an infant with tuberous sclerosis (TS).

Methods: We applied a multiple band frequency analysis to video electroencephalographic (EEG) recordings of the infant's scalp. We also performed computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and magnetoencephalography (MEG) of the brain in order to ascertain the epileptic focus.

Importance of CAG repeat length in childhood-onset dentatorubral-pallidoluysian atrophy.

To elucidate a relationship between CAG repeat expansion length and disease progression history in patients with childhood-onset dentatorubral-pallidoluysian atrophy (DRPLA). We retrospectively evaluated information from nine Japanese patients with disease onset reported as between 6 months and 12 years of age. CAG repeat length in these patients ranged from 62 to 93.

Neuronal subtype specification in the cerebellum and dorsal hindbrain.

In the nervous system, there are hundreds to thousands of neuronal cell types that have morphologically, physiologically, and histochemically different characteristics and this diversity may enable us to elicit higher brain function. A better understanding of the molecular machinery by which neuron subtype specification occurs is thus one of the most important issues in brain science. The dorsal hindbrain, including the cerebellum, is a good model system to study this issue because a variety of types of neurons are produced from this region.

Professional Caregiver's View on Mental Health in Parents of Children with Developmental Disabilities: A Nationwide Study of Institutions and Consultation Centers in Japan.

Parents of children with intellectual disabilities and/or physical disabilities are supposed to have an increased risk for parenting stress and psychological distress. We as professional caregivers sometimes experience difficulties in keeping good relations or communicating with the parents. Professional workers in 460 institutions and consultation centers throughout Japan answered a questionnaire on their clinical experiences.

A case of bulbar type cerebral palsy: representative symptoms of dorsal brainstem syndrome.

In this study, we present the case of a 2-year-old boy who exhibited facial and bulbar paralysis since birth, severe dysphagia, signs of oculomotor disturbance, jaw jerks, pyramidal signs on both toes, intellectual disability, and severe gastroesophageal reflux. His blink reflex and auditory/somatosensory evoked potentials suggested abnormalities in the lower brainstem, and magnetic resonance imaging showed a T2 hyperintense area in the pontine tegmentum. These findings combined with the patient's symptoms suggested "dorsal brainstem syndrome" and indicated a possibility of prenatal asphyxia in this patient.

[Developmental changes of rapid automatized naming and Hiragana reading of Japanese in elementary-school children].

Two hundred and seven Japanese elementary school children aged from 6 (Grade 1) to 12 (Grade 6) years old were tested for their abilities to name numbers and pictured objects along with reading Hiragana characters and words. These children all showed typical development and their classroom teachers judged that they were not having any problems with reading or writing. The children were randomly divided into two groups, the first group was assigned to two naming tasks;the rapid automatized naming (RAN) of "numbers" and "pictured objects," the second group was assigned to two rapid alternative stimulus (RAS) naming tasks using numbers and pictured objects.

Reduced prefrontal hemodynamic response in children with ADHD during the Go/NoGo task: a NIRS study.

The current study examined the hemodynamic response during the Go/NoGo task in children with/without attention deficit/hyperactivity disorder (ADHD). Using near-infrared spectroscopy, oxy-Hb and deoxy-Hb concentration changes in the frontal areas were compared during the conditions with/without inhibitory demand. Compared with typically developing children, children with ADHD showed significantly reduced activation during the conditions with inhibitory demand (NoGo-condition) in the frontal areas.

Characterization of the Asian myopathy patients with VCP mutations.

Background And Purpose: Mutations in the valosin-containing protein (VCP) gene are known to cause inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and familial amyotrophic lateral sclerosis (ALS). Despite an increasing number of clinical reports, only one Asian family with IBMPFD has been described.

Methods: To characterize patients with VCP mutations, we screened a total of 152 unrelated Asian families who were suspected to have rimmed vacuolar myopathy.

Deep brain stimulation for Tourette syndrome: a prospective pilot study in Japan.

Objective: Refractory Tourette syndrome (TS) disturbs the social life of patients. Deep brain stimulation (DBS) has recently been applied to relieve severe tics. We report a prospective open-labeled case series of DBS for TS as a pilot study.

MicroRNA function and neurotrophin BDNF.

MicroRNAs (miRs), endogenous small RNAs, regulate gene expression through repression of translational activity after binding to target mRNAs. miRs are involved in various cellular processes including differentiation, metabolism, and apoptosis. Furthermore, possible involvement of miRs in neuronal function have been proposed.