Early Exposure of Fosphenytoin, Levetiracetam, and Valproic Acid After High-Dose Intravenous Administration in Young Children With Benzodiazepine-Refractory Status Epilepticus.

Fosphenytoin (FOS) and its active form, phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA) are commonly used second-line treatments of status epilepticus. However, limited information is available regarding LEV and VPA concentrations following high intravenous doses, particularly in young children. The Established Status Epilepticus Treatment Trial, a blinded, comparative effectiveness study of FOS, LEV, and VPA for benzodiazepine-refractory status epilepticus provided an opportunity to investigate early drug concentrations. Patients aged ≥2 years who continued to seizure despite receiving adequate doses of benzodiazepines were randomly assigned to FOS, LEV, or VPA infused over 10 minutes. A sparse blood-sampling approach was used, with up to 2 samples collected per patient within 2 hours following drug administration. The objective of this work was to report early drug exposure of PHT, LEV, and VPA and plasma protein binding of PHT and VPA. Twenty-seven children with median (interquartile range) age of 4 (2.5-6.5) years were enrolled. The total plasma concentrations ranged from 69 to 151.3 µg/mL for LEV, 11.3 to 26.7 µg/mL for PHT and 126 to 223 µg/mL for VPA. Free fraction ranged from 4% to 19% for PHT and 17% to 51% for VPA. This is the first report in young children of LEV concentrations with convulsive status epilepticus as well as VPA concentrations after a 40 mg/kg dose. Several challenges limited patient enrollment and blood sampling. Additional studies with a larger sample size are required to evaluate the exposure-response relationships in this emergent condition.

Vitamin D supplementation.

Vitamin D testing and supplementation is of great interest to neurologists and their patients. Recommended nutritional intakes of vitamin D in the UK remain focused on bone health, despite increasing evidence for a role outside this area. Here we discuss how neurologists might approach vitamin D testing and supplementation, focusing on two conditions associated with vitamin D deficiency that have an increased risk of downstream complications resulting from these: multiple sclerosis and epilepsy. We set out a rationale for testing serum 25-hydroxyvitamin D concentrations and discuss our personal practice in terms of supplementation, with evidence where available.

Advances in epilepsy.

Advances in understanding of both the causes and consequences of epilepsy have been paralleled by a number of recent reports and clinical guidelines highlighting the complexities involved in both diagnosing and treating epilepsy. We review recent developments, including comments on the evolution of clinical guidelines, anti-epileptic drugs, epilepsy surgery and new treatment approaches in development. Epilepsy genetics and emerging evidence on mechanisms of drug resistance in epilepsy will also be discussed. Issues with respect to pregnancy and epilepsy are considered, together with more recently identified dilemmas including bone health in epilepsy and whether seizures themselves cause brain damage. Imaging in epilepsy has recently been reviewed elsewhere, and will not be discussed.