Long-term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3-year results from the cannabidiol expanded access program.

Objective: The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC.

Methods: Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d.

Intraoperative Cortical Asynchrony Predicts Abnormal Postoperative Electroencephalogram.

Background: Postoperative electroencephalograms (EEGs) can identify seizure activity and neurologic dysfunction in high-risk neonates requiring cardiac surgical procedures. Although intraoperative EEG monitoring is uncommon, variations in cerebral blood flow and temperature during antegrade cerebral perfusion (ACP) can manifest as cortical asynchrony during EEG monitoring. We hypothesized that intraoperative EEG cortical asynchrony would identify neonates at risk for abnormal postoperative EEG tracings.

Neurodevelopmental Delay After the Neonatal Repair of Coarctation and Arch Obstruction.

Background: Although single ventricle physiology and cyanosis are known risk factors for neurodevelopmental delay (NDD), the impacts of isolated coarctation (Iso CoA) repair or arch reconstruction (AR) are less understood.

Methods: The Vineland Adaptive Behavior Scales, third edition, prospectively evaluated children without a genetic syndrome. An overall composite score, normalized to age and sex, was generated from individual domain scores.

PLXNA1 developmental encephalopathy with syndromic features: A case report and review of the literature.

Developmental encephalopathies constitute a broad and genetically heterogeneous spectrum of disorders associated with global developmental delay, intellectual disability, frequent epilepsy, and other neurofunctional abnormalities. Here, we report a male presenting with infantile onset epilepsy and syndromic features resembling Dubowitz syndrome identified to have a de novo PLXNA1 variant by whole exome sequencing. This constitutes the second report of PLXNA1 sequence variation associated with early onset epilepsy, and the first to expand on the clinical features of this emerging disorder.

Developing a novel epileptic discharge localization algorithm for electroencephalogram infantile spasms during hypsarrhythmia.

Infantile spasms (ISS) is a devastating epileptic syndrome that affects children under the age of 1 year. The diagnosis of ISS is based on the semiology of the seizure and the electroencephalogram (EEG) background characterized by hypsarrhythmia (HYPS). However, even skilled electrophysiologists may interpret the EEG of children with ISS differently, and commercial software or existing epilepsy detection algorithms are not helpful.

Phenotype Differentiation of FOXG1 and MECP2 Disorders: A New Method for Characterization of Developmental Encephalopathies.

Objective: To differentiate developmental encephalopathies by creating a novel quantitative phenotyping tool.

Study Design: We created the Developmental Encephalopathy Inventory (DEI) to differentiate disorders with complex multisystem neurodevelopmental symptoms. We then used the DEI to study the phenotype features of 20 subjects with FOXG1 disorder and 11 subjects with MECP2 disorder.

Automatic localization of epileptic spikes in eegs of children with infantile spasms.

A novel methodology is proposed for identifying epileptiform discharges associated with individuals exhibiting Infantile Spasms (ISS) also known as West Syndrome, which is characterized by electroencephalogram (EEG) recordings exhibiting hypsarrythmia (HYPS). The approach to identify these discharges consists of three stages: first - construct the time-frequency domain (TFD) of the EEG recording using matching pursuit TFD (MP-TFD), second - decompose the TFD matrix into two submatrices (W, H) using non-negative matrix factorization (NMF), and third - use the decomposed spectral and temporal vectors to locate the epileptiform discharges, referred to as spikes, during intervals of HYPS. The method was applied to an EEG dataset of five individuals and the identification of spike locations was compared with those which were visually identified by the epileptologists and those obtained using commercially available clinical analysis software.

Characteristic Features of the Interictal EEG Background in 2 Patients With Malignant Migrating Partial Epilepsy in Infancy.

Purpose: To describe chronological electrographic features of the interictal EEG background observed in two patients with malignant migrating partial epilepsy in infancy from neonatal to early infantile period.

Methods: EEGs of two patients who fulfilled diagnostic criteria for malignant migrating partial epilepsy in infancy were acquired over the period of 6 months to monitor treatment efficacy and characterize seizures and other paroxysmal events.

Results: Both patients followed a similar sequential pattern.

Genetic disorders associated with postnatal microcephaly.

Several genetic disorders are characterized by normal head size at birth, followed by deceleration in head growth resulting in postnatal microcephaly. Among these are classic disorders such as Angelman syndrome and MECP2-related disorder (formerly Rett syndrome), as well as more recently described clinical entities associated with mutations in CASK, CDKL5, CREBBP, and EP300 (Rubinstein-Taybi syndrome), FOXG1, SLC9A6 (Christianson syndrome), and TCF4 (Pitt-Hopkins syndrome). These disorders can be identified clinically by phenotyping across multiple neurodevelopmental and neurobehavioral realms, and enough data are available to recognize these postnatal microcephaly disorders as separate diagnostic entities in their own right.

Epilepsy and outcome in FOXG1-related disorders.

Objective: FOXG1-related disorders are associated with severe intellectual disability, absent speech with autistic features, and epilepsy. Children with deletions or intragenic mutations of FOXG1 also have postnatal microcephaly, morphologic abnormalities of the corpus callosum, and choreiform movements. Duplications of 14q12 often present with infantile spasms, and have subsequent intellectual disability with autistic features.

De novo mutations in the beta-tubulin gene TUBB2A cause simplified gyral patterning and infantile-onset epilepsy.

Tubulins, and microtubule polymers into which they incorporate, play critical mechanical roles in neuronal function during cell proliferation, neuronal migration, and postmigrational development: the three major overlapping events of mammalian cerebral cortex development. A number of neuronally expressed tubulin genes are associated with a spectrum of disorders affecting cerebral cortex formation. Such "tubulinopathies" include lissencephaly/pachygyria, polymicrogyria-like malformations, and simplified gyral patterns, in addition to characteristic extracortical features, such as corpus callosal, basal ganglia, and cerebellar abnormalities.

Neonatal seizures in the era of therapeutic hypothermia: keeping it cool.

The neonatal brain is potentially wired for seizures based on the timing and severity of disease states in the context of vulnerabilities of the immature brain.(1) Seizures in neonates are often the presenting sign of potential brain injury from multiple etiologies, including asphyxia or hypoxic ischemic encephalopathy (HIE). Seizures may also result from diverse causes of neonatal encephalopathy, with those in the neonatal period portending a worse neurodevelopmental prognosis if associated with damage to the developing brain.

Intraoperative electroencephalography predicts postoperative seizures in infants with congenital heart disease.

Background: During the surgical repair of infants with congenital cardiac defects, there can be periods of decreased cerebral blood flow, particularly during deep hypothermic circulatory arrest. As a result, these infants are at increased risk for seizures and long-term neurodevelopmental difficulties.

Methods: Thirty-two infants with congenital heart disease had continuous video-electroencephalographic (EEG) monitoring pre-, intra-, and postoperatively for 48 hours after surgery.