Epilepsy and Anti-Seizure Medications: Secret Agents for Endocrine Disruption.

There is a reciprocal relationship between epilepsy and reproductive endocrine disorders. Seizures and anti-seizure medications (ASMs) can contribute to reproductive and endocrine dysfunction and reproductive dysfunction may exacerbate seizures. Epilepsy via neuroendocrine mechanisms affects the hypothalamic-pituitary-ovarian (HPO) axis, disrupting the regulation of gonadotropin secretion, and resulting in dystrophic effects on the ovaries and early menopause.

Empiric dosing strategies to predict lamotrigine concentrations during pregnancy.

Introduction: Maintaining seizure control with lamotrigine is complicated by altered pharmacokinetics and existence of subpopulations in whom clearance increases or remains constant during pregnancy.

Objective: Our objective was to characterize the potential for particular dosing scenarios to lead to increased seizure risk or toxicity.

Methods: Lamotrigine pharmacokinetic parameters obtained from our previous study were applied to a one-compartment model structure with subpopulations (75:25%) exhibiting different clearance changes.

Capturing seizures in clinical trials of antiseizure medications for -DEE.

Literature review of patients with developmental and epileptic encephalopathy (-DEE) reveals, based on 16 reports including 139 patients, a clinical phenotype that includes age- and disease-specific stereotyped seizures. The typical seizure type of -DEE, focal tonic, starts within 0-5 days of life and is readily captured by video-electroencephalography VEEG for clinical and genetic diagnosis. After initial identification, -DEE seizures are clinically apparent and can be clearly identified without the use of EEG or VEEG.

Lamotrigine clearance increases by 5 weeks gestational age: Relationship to estradiol concentrations and gestational age.

Objective: To determine how early lamotrigine clearance (LTG-CL/F) increases during early pregnancy in women with epilepsy and to quantify the relationship of LTG-CL/F to estradiol concentrations and gestational week.

Methods: This was a multicenter, observational study of pregnant women with epilepsy on lamotrigine and no interacting concomitant medications, employing frequent blood sampling prior to and early in pregnancy. A population mixed-effects modeling approach was used to describe the relationship between LTG-CL/F and gestational week and between LTG-CL/F and estradiol.

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome.

Objective: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome.

Methods: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods.

Epilepsy surgery in patients with autism.

OBJECTIVE The purpose of this study was to report outcomes of epilepsy surgery in 56 consecutive patients with autism spectrum disorder. METHODS Medical records of 56 consecutive patients with autism who underwent epilepsy surgery were reviewed with regard to clinical characteristics, surgical management, postoperative seizure control, and behavioral changes. RESULTS Of the 56 patients with autism, 39 were male, 45 were severely autistic, 27 had a history of clinically significant levels of aggression and other disruptive behaviors, and 30 were considered nonverbal at baseline.

Anti-mullerian hormone is higher in seizure-free women with epilepsy compared to those with ongoing seizures.

Objective: To determine if anti-mullerian hormone (AMH), a neuroactive peptide hormone and a measure of ovarian reserve, is different between women with epilepsy (WWE) and healthy controls (HC) seeking pregnancy and to evaluate epilepsy-related factors associated with AMH concentrations.

Methods: Subjects were participants in Women with Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD), a multi-center prospective, observational cohort study evaluating fecundity in WWE compared to HC, ages 18-40 years. WWE were divided into a Sz+ group or a Sz- group, dependent on whether they had seizures within the 9 months prior to enrollment.

Medication adherence in women with epilepsy who are planning pregnancy.

Objective: This study examines medication adherence among women with epilepsy via use of an electronic diary, as part of a prospective multicenter observational study designed to evaluate fertility in women with epilepsy (WWE) versus age-matched controls.

Methods: WWE and healthy age-matched controls, seeking pregnancy, were given an iPod Touch using a customized mobile application (the WEPOD App) for daily data tracking. Eighty-six WWE tracked seizures and antiepileptic drugs (AEDs).

Do drivers with epilepsy have higher rates of motor vehicle accidents than those without epilepsy?

Objective: We sought to understand the magnitude of the risk that drivers with epilepsy (DWE) contribute to motor vehicle accidents (MVAs) compared to other drivers.

Methods: We performed an evidence-based, systematic review using the American Academy of Neurology (AAN) guideline methodology.

Results: Contributory evidence consisted of six Class II studies and one Class III study.

Gender issues in the neurobiology of epilepsy: a clinical perspective.

A patient's hormonal milieu contributes to the timing of emergence of several epilepsy syndromes that are known to begin at puberty and recede with the end of reproductive potential. One's hormonal balance at any particular moment contributes to seizure occurrence in both men and women. The best studied condition, catamenial epilepsy, refers to seizure clusters occurring in a cyclical pattern related to menses.

Pregnancy and epilepsy.

Purpose Of Review: This review encompasses issues regarding the management of women with epilepsy and pregnancy, including preconception planning, antiepileptic drug (AED) effects on the exposed offspring, and consequences of seizures during pregnancy, with an emphasis on counseling points and risk management.

Recent Findings: In utero valproate exposure continues to show the highest risk of congenital malformations and of adverse cognitive outcomes, including autism, compared to other AEDs. In utero topiramate exposure is associated with facial clefts.