Structural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression.

Background: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints < 5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

Efficacy and Tolerability of Ultra Rapid Duty Cycling Vagus Nerve Stimulation for Medically Refractory Absence Seizures.

Background: Significant knowledge gap exists on vagus nerve stimulation (VNS) efficacy and tolerability in medically refractory absence seizures (MRAS). This retrospective review of patients with MRAS aims to narrow this knowledge gap by comparing ultra rapid duty cycling ([URDC] ON time seven seconds, OFF time 0.2 minutes) with less frequent stimulations of rapid duty cycling (RDC, OFF time <1.

Factors Associated With Growth in Patients Treated With the Classic Ketogenic Diet for Drug-Resistant Epilepsy.

Background: Suboptimal growth and malnutrition are often cited as complications of ketogenic diet therapy in patients with drug-resistant epilepsy; however, there is conflicting evidence on the factors that contribute to growth.

Methods: This is an observational, case-based study to evaluate growth in patients with drug-resistant epilepsy treated with the classic ketogenic diet for at least 12 months. Age, gender, height, weight, and body mass index (BMI) were collected at baseline and epilepsy clinic standard-of-care visits (one month, six months, and 12 months after diet initiation).

The use of virtual tools in narrowing the impact of health disparities in neurology.

The concept of Epilepsy Treatment Gap (ETG) refers to the proportion of people with epilepsy who are not being appropriately treated. The ETG in the USA approaches 10%, with historically underserved populations and rural populations disproportionately affected. The ETG in Low-and Middle-Income Countries (LMIC) is reported to be 5-10 times higher than in high-income countries.

Combined use of the ketogenic diet and vagus nerve stimulation in pediatric drug-resistant epilepsy.

Objective: Patients with drug-resistant epilepsy (DRE) pose considerable management challenges for patients, their families, and providers. Both the vagus nerve stimulator (VNS) and the ketogenic diet (KD) have been shown to be safe and effective in treating DRE. Nevertheless, information is lacking regarding treatment with combination of both modalities.

The efficacy and tolerability of auto-stimulation-VNS in children with Lennox-Gastaut syndrome.

Objective: Lennox-Gastaut syndrome (LGS) is a severe drug-resistant epilepsy (DRE) of childhood. The Vagus Nerve Stimulator (VNS) is established as a safe and effective treatment for DRE. This study assesses efficacy and tolerability of the auto-stimulation VNS models in pediatric patients with LGS.

The Efficacy and Safety of Rapid Cycling Vagus Nerve Stimulation in Children With Intractable Epilepsy.

Purpose: Vagus nerve stimulation (VNS) is an effective adjunctive therapy for drug-resistant epilepsy. Nevertheless, information is lacking regarding optimization of stimulation parameters to improve efficacy. Our study examines the safety and efficacy of rapid duty cycle VNS (OFF time ≤1.

Safety and tolerability of adjunctive lacosamide in a pediatric population with focal seizures - An open-label trial.

Purpose: To evaluate safety and tolerability of adjunctive lacosamide in children with focal seizures.

Methods: Patients were eligible for this open-label, fixed-titration trial (SP0847; NCT00938431) if aged 1 month-17 years with focal seizures taking 1-3 antiepileptic drugs. Findings from Cohort 1, aged 5-11 years, who received lacosamide ≤8 mg/kg/day, informed dosing for age-based cohorts 2-5, who then received ≤12 mg/kg/day (≤600 mg/day).

Initiating the ketogenic diet in infants with treatment refractory epilepsy while maintaining a breast milk diet.

Purpose: The ketogenic diet has been found to be safe and effective in the treatment of drug resistant epilepsy in childhood. The age range of children undergoing this treatment has steadily been going down. There is strong evidence that it is a safe alternative in infants with drug resistant seizures.

Electroclinical Features of Generalized Paroxysmal Fast Activity in Typical Absence Seizures.

Purpose: Generalized paroxysmal fast activity (GPFA) is a diffuse, paroxysmal, frontal predominant activity described in patients with generalized epilepsies. Studies specifically focusing on electroclinical features of typical absence seizures in children have not reported any GPFA-like features. We sought to identify GPFA in children with typical absence seizures, study its incidence, characteristic electroclinical features, and effect on their epilepsy.

Hypotonia and intellectual disability without dysmorphic features in a patient with PIGN-related disease.

Background: Defects in the human glycosylphosphatidylinositol anchor biosynthetic pathway are associated with inherited glycosylphosphatidylinositol (GPI)-deficiencies characterized by a broad range of clinical phenotypes including multiple congenital anomalies, dysmorphic faces, developmental delay, hypotonia, and epilepsy. Biallelic variants in PIGN, encoding phosphatidylinositol-glycan biosynthesis class N have been recently associated with multiple congenital anomalies hypotonia seizure syndrome.

Case Presentation: Our patient is a 2 year old male with hypotonia, global developmental delay, and focal epilepsy.

Ketogenic Diet Decreases Emergency Room Visits and Hospitalizations Related to Epilepsy.

. Approximately, one-third of patients with epilepsy are refractory to pharmacological treatment which mandates extensive medical care and imposes significant economic burden on patients and their societies. This study intends to assess the impact of the treatment with ketogenic diet (KD) on reducing seizure-related emergency room visits and hospitalizations in children with refractory epilepsy.

PCDH19-related epileptic encephalopathy in a male mosaic for a truncating variant.

Variants in the X-linked gene PCDH19 are associated with early infantile epileptic encephalopathy-9. This unusual condition spares hemizygous males except for psychiatric and behavioral abnormalities, and for this reason is also known as female limited epilepsy. Some cases are due to de novo PCDH19 variants, but may also be paternally inherited.

Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.

Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown.

Management of symptomatic cholelithiasis while on ketogenic diet: a case report.

Introduction: The ketogenic diet is a treatment modality used for patients with refractory epilepsy. Development of cholelithiasis while on the ketogenic diet is a potential side effect that has been described in the literature. There however have not been any reports on the outcomes of continuing the diet after cholecystectomy.

The role of epilepsy surgery in the treatment of childhood epileptic encephalopathy.

Children with epileptic encephalopathy often have global impairment of brain function and frequent intractable seizures, which contribute further to their developmental disability. Many of these children have identifiable brain lesion on neurological imaging. In such cases, epilepsy surgery may be considered as a treatment option despite the lack of localized epileptic pattern on electroencephalogram (EEG).

15q11.2 proximal imbalances associated with a diverse array of neuropsychiatric disorders and mild dysmorphic features.

Deletion within the proximal region of chromosome 15q11.2 between breakpoints 1 and 2 (BP1-BP2) has been proposed to be a risk factor for intellectual disability, seizure, and schizophrenia. However, the clinical significance of its reciprocal duplication is not clearly defined yet.

1.39 Mb inherited interstitial deletion in 12p13.33 associated with developmental delay.

We identified a novel 1.39 Mb interstitial deletion of chromosome 12p13.33 in an 8 year-old Caucasian female propositus and her affected father and brother using microarray-based comparative genomic hybridization (aCGH).

Incidental neuroimaging findings in nonacute headache.

We studied the frequency and consequences of incidental neuroimaging findings in 400 otherwise healthy, nonacute pediatric headache patients through a retrospective, cross-sectional analysis. We excluded patients with currently recommended clinical criteria to consider diagnostic neuroimaging. We categorized neuroimaging results as normal, remarkable without clinical action, remarkable with clinical follow-up action, and abnormal.

Cerebral venous thrombosis after immune thrombocytopenic purpura and anti-D immune globulin therapy.

Cerebral venous thrombosis has multiple etiologies and a wide variety of clinical manifestations. This article reports on a young girl who developed cerebral venous thrombosis after intravenous anti-D immune globulin therapy for immune thrombocytopenic purpura. In this case, venous infarction was manifested by an unusual pattern of restricted diffusion limited to the corpus callosum.