Time to onset of cannabidiol (CBD) treatment effect in Lennox-Gastaut syndrome: Analysis from two randomized controlled trials.

Objective: To estimate time to onset of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]), we conducted post hoc analyses of data from two randomized, placebo-controlled, Phase 3 trials, GWPCARE3 (NCT02224560) and GWPCARE4 (NCT02224690), of patients with Lennox-Gastaut syndrome.

Methods: Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex, 100 mg/ml oral solution) at 10 mg/kg/day (CBD10; GWPCARE3) or 20 mg/kg/day (CBD20; both trials) or placebo for 14 weeks. Treatment started at 2.

Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs.

Highly purified cannabidiol (CBD) has demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome in randomized, double-blind, add-on, controlled phase 3 trials. It is important to consider the possibility of drug-drug interactions (DDIs). Here, we review six trials of CBD (Epidiolex/Epidyolex; 100 mg/mL oral solution) in healthy volunteers or patients with epilepsy, which investigated potential interactions between CBD and enzymes involved in drug metabolism of common antiseizure drugs (ASDs).

A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug-Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy.

Background: In recent randomized, placebo-controlled, phase III trials, highly purified cannabidiol demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome. It is anticipated that antiepileptic drugs such as stiripentol and valproate will be administered concomitantly with cannabidiol.

Objectives: This trial evaluated the effect of cannabidiol on steady-state pharmacokinetics of stiripentol or valproate in patients with epilepsy, and the safety and tolerability of cannabidiol.

Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.

Background: Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy.

Methods: In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox-Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks.

Lamotrigine extended-release as adjunctive therapy with optional conversion to monotherapy in older adults with epilepsy.

Purpose: To determine the tolerability and efficacy of lamotrigine extended-release (LTG XR) as adjunctive therapy with optional conversion to monotherapy in patients ages≥65 years with epilepsy.

Methods: This open-label study included the standard LTG XR dose escalation, an 8-week Adjunctive Maintenance Phase (AMP), a 13-week Adjunctive Optimization Phase or Conversion and Monotherapy Phase, and a Taper/Follow-Up Phase. At the end of the AMP, patients on a single concomitant antiepileptic drug (AED) were converted to LTG XR monotherapy over 5 weeks and then remained in the Monotherapy Maintenance Phase for 8 weeks.

Safety and efficacy of ezogabine (retigabine) in adults with refractory partial-onset seizures: Interim results from two ongoing open-label studies.

Interim results of two open-label extension studies assessed ezogabine/retigabine safety and tolerability for partial-onset seizures. At data cutoff, 336 (60%) patients received ≥ 12 months' open-label ezogabine/retigabine. The most common TEAEs included dizziness (22%), somnolence (19%), headache (14%), and fatigue (10%).

The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels.

Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; North American adopted name), a first-in-class antiepileptic drug (AED) that reduces neuronal excitability primarily by enhancing the activity of KCNQ2/3 (K(v)7.2/7.3) potassium channels, has recently been approved by the European Medicines Agency and the U.

Effects of lamotrigine and phenytoin on the pharmacokinetics of atorvastatin in healthy volunteers.

Purpose: Statins and antiepileptic drugs (AEDs) are frequently coprescribed to individuals with hypercholesterolemia and new-onset seizures. Statins are metabolized by the cytochrome P450 (CYP) enzyme system. Interactions between statins and agents that undergo CYP metabolism are common.

Clinical and imaging findings suggesting human herpesvirus 6 encephalitis.

We sought to distinguish patients testing positive for human herpesvirus 6 from those testing negative, based on clinical features and magnetic resonance images. Sixteen immunosuppresed patients were tested by polymerase chain reaction for human herpes virus 6 DNA in cerebrospinal fluid (nine positive results). Medical records were examined for agitation, altered mental status, hallucinations, insomnia, memory loss, and seizures.

Extrahippocampal involvement in human herpesvirus 6 encephalitis depicted at MR imaging.

Purpose: To test the hypothesis that patterns of signal intensity abnormality in human herpesvirus 6 (HHV6)-positive patients would allow distinction from patients who did not test positive for HHV6 encephalitis.

Materials And Methods: This retrospective study was performed with institutional review board committee approval by using a waiver of informed consent. Sixteen immunocompromised patients (nine males, seven females; age range, 2-39 years) underwent magnetic resonance (MR) imaging and cerebrospinal fluid polymerase chain reaction (PCR) testing for HHV6 DNA on the basis of clinical findings suspicious for encephalitis.

Hippocampal MRI signal hyperintensity after febrile status epilepticus is predictive of subsequent mesial temporal sclerosis.

Objective: The objective of our study was to test the hypothesis that the finding of hyperintense hippocampal signal intensity on T2-weighted MR images soon after febrile status epilepticus is associated with subsequent hippocampal volume loss and persistent abnormal signal intensity on T2-weighted images (i.e., mesial temporal sclerosis).

Do prolonged febrile seizures produce medial temporal sclerosis? Hypotheses, MRI evidence and unanswered questions.

Whether or not severe febrile seizures in infancy cause hippocampal injury and subsequent medial temporal sclerosis is an often debated question in epilepsy. Recent magnetic resonance imaging (MRI) of infants suffering from febrile seizures has provided preliminary evidence that abnormally increased T2 signal intensity can be seen in the hippocampi of infants following prolonged and focal febrile seizures. Follow-up MRIs in a few of these infants have confirmed that medial temporal sclerosis can develop following these acute MRI signal changes.

Reflex seizures and non-ketotic hyperglycemia: an unresolved issue.

Reflex seizures are a rare form of epilepsy, the pathogenesis of which is unclear. They have been reported in the setting of non-ketotic hyperglycemia (NKH) and are considered to be neuroendocrine in origin. We report a diabetic patient with movement-induced seizures whose presentation suggests that brain ischemia may be the precipitating event in focal seizures seen in the setting of NKH.