A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor.

Background: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABA receptors.

Objective: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET).

Methods: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days.

Efficacy, safety, and tolerability of soticlestat as adjunctive therapy for the treatment of seizures in patients with Dup15q syndrome or CDKL5 deficiency disorder in an open-label signal-finding phase II study (ARCADE).

Objective: Chromosome 15q duplication (Dup15q) syndrome and cyclin‑dependent kinase-like 5 deficiency disorder (CDD) are rare neurodevelopmental disorders associated with epileptic encephalopathies, with a lack of specifically approved treatment options. ARCADE assessed the efficacy and safety of adjunctive soticlestat (TAK-935) for the treatment of seizures in patients with Dup15q syndrome or CDD (NCT03694275).

Methods: ARCADE was a phase II, open-label, pilot study of soticlestat (≤300 mg/day twice daily, weight-adjusted) in pediatric and adult patients 2-55 years of age with Dup15q syndrome or CDD who experienced ≥3 motor seizures per month in the 3 months before screening and at baseline.

Randomized controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in adults with complex regional pain syndrome.

Objective: The objective was to investigate the efficacy and safety of soticlestat as adjunctive therapy in participants with complex regional pain syndrome (CRPS).

Design: A proof-of-concept phase 2a study, comprising a 15-week randomized, double-blind, placebo-controlled, parallel-group study (part A), and an optional 14-week open-label extension (part B).

Methods: Twenty-four participants (median age 44.

A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in pediatric patients with Dravet syndrome or Lennox-Gastaut syndrome (ELEKTRA).

Objective: Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare treatment-resistant childhood epilepsies classed as developmental and epileptic encephalopathies. ELEKTRA investigated the efficacy and safety of soticlestat (TAK-935) as adjunctive therapy in children with DS or LGS (NCT03650452).

Methods: ELEKTRA was a phase 2, randomized, double-blind, placebo-controlled study of soticlestat (≤300 mg twice daily, weight-adjusted) in children (aged 2-17 years) with DS, demonstrating three or more convulsive seizures/month, or with LGS, demonstrating four or more drop seizures/month at baseline.

A phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK-041 in healthy participants and patients with stable schizophrenia.

Aims: TAK-041 (NBI-1065846), an orally available, investigational, small molecule agonist of GPR139, an orphan G-protein-coupled receptor, has shown promise in preclinical studies for the treatment of symptoms associated with schizophrenia. Here, we report the results from a phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK-041 in healthy adults and exploratory efficacy assessment of TAK-041 as adjunctive therapy to antipsychotics in adults with stable schizophrenia (ClinicalTrials.gov: NCT02748694).

Safety, pharmacokinetics and pharmacodynamics of TAK-418, a novel inhibitor of the epigenetic modulator lysine-specific demethylase 1A.

Aims: Dysregulation of histone methylation epigenetic marks may result in intellectual and developmental disability, as seen in Kabuki syndrome. Animal data suggest that increasing histone methylation by inhibiting lysine-specific demethylase 1A (LSD1) may improve cognitive outcomes in a model of Kabuki syndrome. TAK-418 is a novel LSD1 inhibitor, developed as a potential therapeutic agent for central nervous system disorders such as Kabuki syndrome.

A phase 1b/2a study of soticlestat as adjunctive therapy in participants with developmental and/or epileptic encephalopathies.

Objective: To evaluate the safety, tolerability, and pharmacokinetics of soticlestat, a first-in-class cholesterol 24-hydroxylase inhibitor, in adults with developmental and/or epileptic encephalopathies (DEE).

Methods: The study comprised a 30-day, randomized, double-blind, placebo-controlled phase (Part A), followed by a 55-day open-label phase (Part B) (ClinicalTrials.gov ID: NCT03166215) .

In Vitro Metabolism of Slowly Cleared G Protein-Coupled Receptor 139 Agonist TAK-041 Using Rat, Dog, Monkey, and Human Hepatocyte Models (HepatoPac): Correlation with In Vivo Metabolism.

Hepatic metabolism of low-clearance compound TAK-041 was studied in two different in vitro model systems using rat, dog, monkey, and human suspended cryopreserved hepatocytes and HepatoPac micropatterned coculture model primary hepatocytes. The aim of this work was to investigate the most appropriate system to assess the biotransformation of TAK-041, determine any notable species difference in the rate and in the extent of its metabolic pathways, and establish correlation with in vivo metabolism. TAK-041 exhibited very low turnover in suspended cryopreserved hepatocyte suspensions for all species, with no metabolites observed in human hepatocytes.

Emergency Department Use of Neuroimaging in Children and Adolescents Presenting with Headache.

Objectives: To evaluate emergency department use and outcomes of neuroimaging for headache in a free-standing children's hospital system.

Study Design: We prospectively enrolled children aged 6-18 years who presented to the emergency department with a chief complaint of headache from September 2015 to September 2016. Standardized data collection was performed in real time, including telephone follow-up as needed, and imaging outcome was determined through a chart review.

Multisite Semiautomated Clinical Data Repository for Duplication 15q Syndrome: Study Protocol and Early Uses.

Background: Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a rare disorder caused by duplications of chromosome 15q11.

Ketogenic diet: Predictors of seizure control.

Background: The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet.

Methods: A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012.

Electroencephalographic patterns during sleep in children with chromosome 15q11.2-13.1 duplications (Dup15q).

Our objective was to define the EEG features during sleep of children with neurodevelopmental disorders due to copy number gains of 15q11-q13 (Dup15q). We retrospectively reviewed continuous EEG recordings of 42 children with Dup15q (mean age: eight years, 32 with idic15), and data collected included background activity, interictal epileptiform discharges, sleep organization, and ictal activity. Three patterns were recognized: Pattern 1: Alpha–delta sleep was noted in 14 children (33%), not associated with any clinical changes.

Clinical experience of intravenous lacosamide in infants and young children.

Objective: To review our clinical experience with intravenous (iv) lacosamide (LCM) in children less than 12 years old.

Background: Use of LCM to treat children with epilepsy has been supported by multiple studies with limited information on iv use in children.

Designs/methods: All children given iv LCM were identified from 2009 to 2015.

A Potential Role for Felbamate in TSC- and NF1-Related Epilepsy: A Case Report and Review of the Literature.

A 15-year-old girl with maternal inheritance of neurofibromatosis type 1 (NF1) and paternal inheritance of tuberous sclerosis complex (TSC) developed intractable epilepsy at age 5. Her seizures were refractory to adequate doses of four antiepileptic medications until felbamate was initiated at age 7. She has since remained seizure-free on felbamate monotherapy.

Pregnancy and neurodevelopmental outcomes with in-utero antiepileptic agent exposure. A pilot study.

Objective: To assess pregnancy outcomes on women exposed to monotherapy with antiepileptic agents.

Methods: Questionnaires were sent to women with epilepsy in our practice who were pregnant between 2006 and 2011. 62/86 patients (72%) who responded were on monotherapy.

Time interval required for return to baseline of the background rhythm on electroencephalogram after recorded electrographic seizures.

Our objective was to assess the time interval that is required for the return to baseline of the background rhythm in the electroencephalogram (EEG) after ictal electrographic activity. We completed a retrospective EEG review of 28 adults and 13 children admitted to the epilepsy monitoring unit at Massachusetts General Hospital. EEG background rhythm on admission was considered the baseline rhythm per patient.

Diverse seizure presentation of acute Mycoplasma pneumoniae encephalitis resolving with immunotherapy.

We report 3 previously normal children that presented for evaluation of new onset seizures. Case 1, a 7-year-old female, presented with refractory left frontal lobe seizures associated with right arm simple motor seizures refractory to 6 antiepileptic medications at sufficient doses and levels. Case 2, a 15-year-old female, presented with left frontotemporal lobe seizures and nonconvulsive seizures, associated with neuropsychiatric symptoms refractory to 5 antiepileptic medications.

Urgent referrals for seizure evaluation to a tertiary care neurology center: a pilot study.

This study evaluates the outcome of urgent neurologic referrals. This was a retrospective review of all referrals to the Floating Hospital for Children in 1 month. The total number of patients referred to our center was 223.