Baseline characteristics and predictors for early implantation of vagus nerve stimulation therapy in people with drug-resistant epilepsy: Observations from an international prospective outcomes registry (CORE-VNS).

Objective: Vagus nerve stimulation (VNS) Therapy is routinely indicated for people with drug-resistant epilepsy (DRE). We analyzed the baseline characteristics of individuals receiving the recently released VNS models and identified factors associated with early or late implantation.

Methods: The Comprehensive Outcomes Registry of subjects with Epilepsy (CORE-VNS), a prospective observational study evaluating the clinical and psychosocial outcomes of VNS Therapy®, is following participants for up to 60 months after VNS implantation.

Focal Epilepsy in Individuals with Laron Syndrome.

Objective: The aim of the study was to describe focal epilepsy in patients with Laron syndrome (LS).

Methods: Data were retrieved from medical records of a single-center cohort of 75 patients with LS.

Results: We describe for the first time 4 patients with concomitant focal epilepsy and LS.

Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy.

Objective: The MAST family of microtubule-associated serine-threonine kinases (STKs) have distinct expression patterns in the developing and mature human and mouse brain. To date, only MAST1 has been conclusively associated with neurological disease, with de novo variants in individuals with a neurodevelopmental disorder, including a mega corpus callosum.

Methods: Using exome sequencing, we identify MAST3 missense variants in individuals with epilepsy.

Epilepsy and electroencephalogram evolution in YWHAG gene mutation: A new phenotype and review of the literature.

A male patient with a de novo mutation in the YWHAG gene and mild phenotype is presented. He had normal delivery and normal development, with normal speech and social milestones. At the age of 9 months, myoclonic seizures started, with generalized epileptiform discharges.

A de novo GABRA2 missense mutation in severe early-onset epileptic encephalopathy with a choreiform movement disorder.

Background: Early-onset epileptic encephalopathy (EOEE) is a severe convulsive disorder with a poor developmental prognosis. Although it has been associated with mutations in a number of genes, the fact that there is a large proportion of patients who remain undiagnosed suggests that there are many more still-unknown genetic causes of EOEE. Achieving a genetic diagnosis is important for understanding the biological basis of the disease, with its implications for treatment and family planning.

Polymicrogyria and myoclonic epilepsy in autosomal recessive cutis laxa type 2A.

Cutis laxa syndromes are rare inherited disorders of skin and connective tissue metabolism associated with variable systemic involvement. The main clinical manifestation is loose, wrinkled, redundant, inelastic skin, hypotonia, typical facies including short nose and down-slanting palpebral fissures, and varying degrees of developmental delay. The aim of this report is to describe two siblings diagnosed with a moderate form of ATP6V0A2-related cutis laxa with polymicrogyria (cobblestone-like brain dysgenesis).

RARS2 mutations cause early onset epileptic encephalopathy without ponto-cerebellar hypoplasia.

Introduction: Early onset epileptic encephalopathies (EOEEs) are a group of devastating diseases, manifesting in the first year of life with frequent seizures and/or prominent interictal epileptiform discharges on the electroencephalogram, developmental delay or regression and usually a poor prognosis. There are numerous causes for EOEEs making the diagnostic workup time consuming and costly.

Methods: We describe two siblings with fatal EOEE, profound global developmental delay and post-natal microcephaly that underwent extensive biochemical and metabolic workup in vain.

Multiplex families with epilepsy: Success of clinical and molecular genetic characterization.

Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis.

Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis.

De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing.

The voltage-gated Kv2.1 potassium channel encoded by KCNB1 produces the major delayed rectifier potassium current in pyramidal neurons. Recently, de novo heterozygous missense KCNB1 mutations have been identified in three patients with epileptic encephalopathy and a patient with neurodevelopmental disorder.

Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome.

Objective: We evaluated seizure outcome in a large cohort of familial neonatal seizures (FNS), and examined phenotypic overlap with different molecular lesions.

Methods: Detailed clinical data were collected from 36 families comprising two or more individuals with neonatal seizures. The seizure course and occurrence of seizures later in life were analyzed.

Endocrine Effects of Valproate versus Carbamazepine in Males with Epilepsy: A Prospective Study.

Background/aims: To prospectively evaluate the long-term impact of valproate (VPA) versus carbamazepine (CBZ) on anthropometric, hormonal, and metabolic parameters in young male patients treated for epilepsy.

Methods: Of 61 boys with newly diagnosed epilepsy followed up, 24 were excluded from analysis (17 were lost to follow-up and 7 changed therapy within <1 year). Findings were compared by time, treatment (VPA or CBZ), and epilepsy type (generalized or partial) as well as against a matched control group with adequately treated hypothyroidism.

Thiamine deficiency in infancy: long-term follow-up.

Background: In 2003, several hundred Israeli infants risked thiamine deficiency after being fed a soy-based formula deficient in thiamine. Approximately 20 patients were seriously affected, and three of them died. We report the clinical presentation of acute encephalopathy in 11 children and the long-term sequelae of eight children who initially survived.

Endocrine effects of valproic acid therapy in girls with epilepsy: a prospective study.

Background/aim: It is controversial whether the endocrine dysfunction in epilepsy patients is caused by the epilepsy itself, the antiepileptic therapy, or both. We prospectively evaluated the long-term impact of valproic acid monotherapy compared to other anti-epileptic drugs on anthropometric, metabolic, hormonal, and ultrasonographic parameters in girls with epilepsy.

Methods: Fifty-seven female patients with epilepsy who had started therapy at mean age of 11.

Early onset epileptic encephalopathy caused by de novo SCN8A mutations.

Objective: De novo SCN8A mutations have been reported in patients with epileptic encephalopathy. Herein we report seven patients with de novo heterozygous SCN8A mutations, which were found in our comprehensive genetic analysis (target capture or whole-exome sequencing) for early onset epileptic encephalopathies (EOEEs).

Methods: A total of 163 patients with EOEEs without mutations in known genes, including 6 with malignant migrating partial seizures in infancy (MMPSI), and 60 with unclassified EOEEs, were analyzed by target capture (28 samples) or whole-exome sequencing (135 samples).

Paternal germline mosaicism of a SCN2A mutation results in Ohtahara syndrome in half siblings.

Ohtahara syndrome is a devastating early infantile epileptic encephalopathy caused by mutations in different genes. We describe a patient with Ohtahara syndrome who presented on the first day of life with refractory tonic seizures and a suppression-burst pattern on EEG. The patient developed severe microcephaly, and never achieved any developmental milestones.

Glutamate receptor antibodies directed against AMPA receptors subunit 3 peptide B (GluR3B) can be produced in DBA/2J mice, lower seizure threshold and induce abnormal behavior.

Objective: Anti-GluR3B antibodies (GluR3B Ab's), directed against peptide B/aa372-395 of GluR3 subunit of glutamate/AMPA receptors, are found in ∼35% of epilepsy patients, activate glutamate/AMPA receptors, evoke ion currents, kill neurons and damage the brain. We recently found that GluR3B Ab's also associate with neurological/psychiatric/behavioral abnormalities in epilepsy patients. Here we asked if GluR3B Ab's could be produced in DBA/2J mice, and also modulate seizure threshold and/or cause behavioral/motor impairments in these mice.

Glutamate receptor antibodies directed against AMPA receptors subunit 3 peptide B (GluR3B) associate with some cognitive/psychiatric/behavioral abnormalities in epilepsy patients.

Antibodies (Ab's) to glutamate receptors, directed specifically against AMPA receptors subunit 3 peptide B (i.e. GluR3 amino acids 372-395), named GluR3B Ab's, can by themselves activate GluR3-containing glutamate/AMPA receptors, evoke ion currents via the receptor's ion channel, kill neurons and damage the brain.

Broad phenotypic heterogeneity due to a novel SCN1A mutation in a family with genetic epilepsy with febrile seizures plus.

Genetic (generalized) epilepsy with febrile seizures plus is a familial epilepsy syndrome with marked phenotypic heterogeneity ranging from simple febrile seizure to severe phenotypes. Here we report on a large Israeli family with genetic (generalized) epilepsy with febrile seizures plus and 14 affected individuals. A novel SCN1A missense mutation in exon 21 (p.

Idiopathic photosensitive occipital epilepsy: clinical and electroencephalographic (EEG) features.

Idiopathic photosensitive occipital lobe epilepsy is a reflex, age- and localization-related syndrome. We describe the clinical and electroencephalographic features, therapy, and outcome of 16 children/adolescents with this syndrome. The cohort included 2 sets of siblings and 7 patients with other first- or second-degree relatives with a seizure history.

Glucose transporter 1 deficiency in the idiopathic generalized epilepsies.

Objective: We examined whether glucose transporter 1 (GLUT1) deficiency causes common idiopathic generalized epilepsies (IGEs).

Methods: The IGEs are common, heritable epilepsies that usually follow complex inheritance; currently little is known about their genetic architecture. Previously considered rare, GLUT1 deficiency, due to mutations in SLC2A1, leads to failure of glucose transport across the blood-brain barrier and inadequate glucose for brain metabolism.

Levetiracetam in children, adolescents and young adults with intractable epilepsy: efficacy, tolerability and effect on electroencephalogram--a pilot study.

Levetiracetam has been authorized for use in Israel as an add-on therapy for intractable epilepsy since May 2006. The aim of the present study was to document its effectiveness for this indication in children, adolescents, and young adults. The medical files of 78 patients aged 0.

PRRT2 phenotypic spectrum includes sporadic and fever-related infantile seizures.

Objective: Benign familial infantile epilepsy (BFIE) is an autosomal dominant epilepsy syndrome characterized by afebrile seizures beginning at about 6 months of age. Mutations in PRRT2, encoding the proline-rich transmembrane protein 2 gene, have recently been identified in the majority of families with BFIE and the associated syndrome of infantile convulsions and choreoathetosis (ICCA). We asked whether the phenotypic spectrum of PRRT2 was broader than initially recognized by studying patients with sporadic benign infantile seizures and non-BFIE familial infantile seizures for PRRT2 mutations.