Displacement of extracellular chloride by immobile anionic constituents of the brain's extracellular matrix.

GABA is the primary inhibitory neurotransmitter. Membrane currents evoked by GABA receptor activation have uniquely small driving forces: their reversal potential (E) is very close to the resting membrane potential. As a consequence, GABA currents can flow in either direction, depending on both the membrane potential and the local intra and extracellular concentrations of the primary permeant ion, chloride (Cl).

Ommaya reservoir placement using ultrasound guidance via anterior fontanelle combined with frameless electromagnetic neuronavigation in patients with mucopolysaccharidosis type 2: Case reports and review of the literature.

Mucopolysaccharidosis type II (MPS II) results from the genetic deficiency of a lysosomal enzyme and is associated with central nervous system (CNS) dysfunction. In Japan, in addition to intravenous enzyme administration, intracerebroventricular enzyme delivery through the Ommaya reservoir has recently gained approval. Nevertheless, the ideal approach for safely implanting the reservoir into the narrow ventricles of infantile MPS II patients remains uncertain.

Nusinersen induces detectable changes in compound motor action potential response in spinal muscular atrophy type 1 patients with severe impairment of motor function.

Background: Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established.

Methods: We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months.

Use of lacosamide for focal epilepsy in a child with kidney failure undergoing peritoneal dialysis.

Background: Lacosamide (LCM) has become commonly used for focal onset seizures due to its high tolerability and low drug interactions. Unlike patients on hemodialysis (HD), pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis (PD) are scant.

Case Report: A 2-year-old girl with end-stage kidney disease undergoing PD suffered prolonged focal onset seizures.

Therapeutic effects of KRM-II-81, positive allosteric modulator for α2/3 subunit containing GABA receptors, in a mouse model of Dravet syndrome.

Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations in the gene, which encodes the α subunit of a voltage-gated Na channel. Pre-synaptic inhibitory dysfunction is regarded as the pathophysiological mechanism, but an effective strategy for ameliorating seizures and behavioral problems is still under development.

Adrenal function during long-term ACTH therapy for patients with developmental and epileptic encephalopathy.

Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long-term ACTH therapy (LT-ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT-ACTH. We evaluated the effectiveness of LT-ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients.

Variance in the pathophysiological impact of the hemizygosity of gamma-aminobutyric acid type A receptor subunit genes between Prader-Willi syndrome and Angelman syndrome.

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 acid type A receptor subunit (GABAaR) genes, while remaining individuals present without the deletion (AS non-Del or PWS non-Del). We previously reported that AS Del, but not AS non-Del individuals, show aberrantly desynchronized somatosensory-evoked magnetic fields (SEFs) and speculated that it might reflect GABAergic dysfunction due to the hemizygosity of GABAaR genes.

Flurothyl-induced seizure paradigm revealed higher seizure susceptibility in middle-aged Angelman syndrome mouse model.

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.

Reinterpretation of magnetic resonance imaging findings with magnetoencephalography can improve the accuracy of detecting epileptogenic cortical lesions.

Objective: This study examined whether the application of magnetoencephalography (MEG) to interpret magnetic resonance imaging (MRI) findings can aid the diagnosis of intractable epilepsy caused by organic brain lesions.

Methods: This study included 51 patients with epilepsy who had MEG clusters but whose initial MRI findings were interpreted as being negative for organic lesions. Three board-certified radiologists reinterpreted the MRI findings, utilizing the MEG findings as a guide.

Short-latency somatosensory-evoked potentials demonstrate cortical dysfunction in patients with Angelman syndrome.

Background: Angelman syndrome (AS) is neurodevelopmental disorder, causal gene of which is maternally expressed . A majority of patients results from the large deletion of relevant chromosome which includes GABA receptor subunit genes (GABARs) as well as (AS Del) We previously reported aberrantly desynchronized primary somatosensory response in AS Del by using magnetoencephalography. The purpose of this study is to estimate cortical and subcortical involvement in the deficit of primary somatosensory processing in AS.

Efficacy of perampanel for epileptic seizures and daily behavior in a patient with Leigh syndrome: A case report.

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 the bilateral striatum on T2-weighted magnetic resonance imaging.

Perampanel for nonepileptic myoclonus in Angelman syndrome.

Background: Angelman syndrome (AS) is a neurodegenerative disorder caused by functional loss of the maternal ubiquitin-protein ligase 3A gene. Nonepileptic myoclonus, also described as tremulous movement, often occurs during puberty and increases in adulthood. The involuntary movement in AS has not been defined patho-physiologically and the drugs used such as levetiracetam and piracetam are not always effective.

Diverse Actions of Astrocytes in GABAergic Signaling.

An imbalance of excitatory and inhibitory neurotransmission leading to over excitation plays a crucial role in generating seizures, while enhancing GABAergic mechanisms are critical in terminating seizures. In recent years, it has been reported in many studies that astrocytes are deeply involved in synaptic transmission. Astrocytes form a critical component of the "tripartite" synapses by wrapping around the pre- and post-synaptic elements.

Long-term follow up of an adult with alternating hemiplegia of childhood and a p.Gly755Ser mutation in the ATP1A3 gene.

Alternating hemiplegia of childhood (AHC) is a rare neurological disease mainly caused by mutations in the ATP1A3 gene and showing varied clinical severity according to genotype. Patients with a p.Gly755Ser (p.

Efficacy of perampanel for controlling seizures and improving neurological dysfunction in a patient with dentatorubral-pallidoluysian atrophy (DRPLA).

We administered perampanel (PER) to a bedridden 13-year-old male patient with dentatorubral-pallidoluysian atrophy (DRPLA). The DRPLA diagnosis was based on the presence of a CAG trinucleotide repeat in the gene. The patient experienced continuous myoclonic seizures and weekly generalized tonic-clonic seizures (GTCs).