Individualized treatment approaches: Fenfluramine, a novel antiepileptic medication for the treatment of seizures in Dravet syndrome.

Dravet syndrome is a rare and severe encephalopathy that first presents in infancy with seizures refractory to conventional antiepileptic drugs. Forty-five percent of patients report four or more tonic-clonic seizures per month despite multidrug regimens. Fenfluramine, an amphetamine derivative, was initially developed as an appetite suppressant with a serotonergic mechanism of action.

PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum.

Background: Primary microcephaly and profound global developmental delay have been considered the core clinical phenotype in patients with bi-allelic mutations.

Methods: Linkage analysis and whole-exome sequencing (WES) in a multiplex family and extraction of further cases from a WES repository containing 571 children with severe developmental disabilities and neurologic symptoms.

Results: We identified bi-allelic mutations in twelve children from six unrelated families.

Extended-release drug formulations for the treatment of epilepsy.

Introduction: Extended-release (ER) preparations are either available or have been tested for several antiepileptic drugs (AEDs). Indeed, they may be helpful in improving efficacy, tolerability, adherence, compared to the corresponding immediate release (IR) preparations available. The use of ER preparations has been advocated in women of childbearing age and is - depending on the drug - especially helpful in patients who are treated in combination with enzyme inducing AEDs as well as in children.

Impact of Hippotherapy on Gross Motor Function and Quality of Life in Children with Bilateral Cerebral Palsy: A Randomized Open-Label Crossover Study.

This study investigated the effect of hippotherapy on gross motor function (Gross Motor Function Measure [GMFM]-66, GMFM dimension E and D) and quality of life (Child Health Questionnaire [CHQ 28], KIDSCREEN-27 parental versions) in children with bilateral spastic cerebral palsy. Seventy-three children (age: 9.1 ± 3.

Effects of the Antiepileptic Drugs Phenytoin, Gabapentin, and Levetiracetam on Bone Strength, Bone Mass, and Bone Turnover in Rats.

Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats.

Effects of the antiepileptic drugs topiramate and lamotrigine on bone metabolism in rats.

Long-term treatment with antiepileptic drugs (AED) is associated with an elevated risk of bone fracture due to decreased bone mineral density (BMD). Phenytoin has been shown to affect bone metabolism adversely, whereas newly developed AEDs have not been studied. This study evaluated the effects of topiramate and lamotrigine on bone metabolism in rats.

Effect of the antidiabetic agent pioglitazone on bone metabolism in rats.

Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor gamma (PPARγ) agonists used as therapy for type 2 diabetes. However, clinical studies reported that the therapeutic modulation of PPARγ activity using TZDs may induce negative effects on bone metabolism. This study aimed to evaluate the effect of the TZD pioglitazone on bone metabolism in rats.

Real-world data on rufinamide treatment in patients with Lennox-Gastaut syndrome: Results from a European noninterventional registry study.

Introduction: Rufinamide is approved for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥4years. The objective of this study was to provide real-world, long-term data on patients with LGS initiating rufinamide as add-on therapy and patients with LGS receiving other antiepileptic drugs (AEDs).

Methods: A Phase IV, noninterventional, multicenter registry study was conducted in patients with LGS aged ≥4years requiring modification to any AED treatment, including initiation of add-on rufinamide therapy.

Health-related quality of life in double-blind Phase III studies of brivaracetam as adjunctive therapy of focal seizures: A pooled, post-hoc analysis.

Purpose: The effect of adjunctive brivaracetam on health-related quality of life (HRQoL) was assessed in a post-hoc analysis using pooled data from three randomized, double-blind, placebo-controlled Phase III studies in patients with refractory focal seizures (NCT00490035, NCT00464269, and NCT01261325).

Methods: The Patient-Weighted Quality of Life in Epilepsy Questionnaire (QOLIE-31-P) was completed at randomization, and weeks 4, 8 (in two of three studies), and 12 (end of the treatment period). Mean change from baseline to week 12 or early discontinuation, and percentage of patients with clinically meaningful improvement were reported for the placebo and brivaracetam 50, 100, and 200mg/day groups.

The 'Photosensitivity Model' is (also) a model for focal (partial) seizures.

The 'Photosensitivity Model' uses a standardized stimulation protocol of repeated intermittent photic stimulation (IPS) over a three-day period, with administration of a single dose of an investigational antiepileptic drug (AED) after a baseline IPS day in photosensitive patients, followed by a third IPS day to determine duration of effect. This 'Photosensitivity Model' has shown its value in the development of new AEDs. Levetiracetam (LEV), currently a first-line AED in new-onset focal epilepsies, was not effective in classical animal models, but showed dose-dependent efficacy in the human 'Photosensitivity Model'.

Brivaracetam as adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy: the current evidence base.

Brivaracetam (BRV) is a novel antiepileptic drug recently licensed for the treatment of partial epilepsy in adults and adolescents over 16 years old. Like levetiracetam (LEV), it is a ligand of the synaptic vesicle protein SV2A. BRV has been shown in animal models and in studies using human brain slices to have a higher SV2A affinity and faster penetration into the brain.

Subjective memory complaints in patients with epilepsy: The role of depression, psychological distress, and attentional functions.

While objective memory dysfunctions have been thoroughly investigated in patients with epilepsy, assessment of subjective memory complaints (SMC) remains challenging. Former studies have demonstrated an impact of patients' depressive mood on SMC. However, the impact of more general psychological distress and cognitive functioning in non-memory domains on SMC has only received little attention so far.

Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes.

Introduction: Despite the success of epilepsy surgery, recent reports suggest a decline in surgical numbers. We tested these trends in our cohort to elucidate potential reasons.

Patients And Methods: Presurgical, surgical and postsurgical data of all patients undergoing presurgical evaluation in between 1990 and 2013 were retrospectively analysed.

Behavioral disorder in people with an intellectual disability and epilepsy: A report of the Intellectual Disability Task Force of the Neuropsychiatric Commission of ILAE.

The management and needs of people with intellectual disability (ID) and epilepsy are well evidenced; less so, the comorbidity of behavioral disorder in this population. "Behavioral disorder" is defined as behaviors that are difficult or disruptive, including stereotypes, difficult or disruptive behavior, aggressive behavior toward other people, behaviors that lead to injury to self or others, and destruction of property. These have an important link to emotional disturbance.

Effect of anticonvulsive treatment on neuropsychological performance in children with BECTS.

Introduction: Benign epilepsy with centrotemporal spikes (BECTS) is a common epilepsy syndrome in childhood. Besides the occurrence of seizures, mild cognitive impairments and behavioral problems affecting language skills, spatial perception, memory, executive function, and academic achievement might be present. There is no international consensus about the decision whether or not to treat affected children.

A noninterventional study evaluating the effectiveness and safety of lacosamide added to monotherapy in patients with epilepsy with partial-onset seizures in daily clinical practice: The VITOBA study.

Objective: Evidence for the efficacy and safety of adjunctive lacosamide in the treatment of partial-onset seizures (POS) was gained during placebo-controlled clinical trials in patients with treatment-resistant seizures who were taking one to three concomitant antiepileptic drugs (AEDs). The VITOBA study (NCT01098162) evaluated the effectiveness and tolerability of adjunctive lacosamide added to one baseline AED in real-world clinical practice.

Methods: We conducted a 6-month observational study at 112 sites across Germany.

A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures.

Objective: Brivaracetam (BRV), a selective and high-affinity synaptic vesicle protein 2A ligand, is in development as adjunctive treatment for partial-onset (focal) seizures (POS). This phase 3 study (N01358; NCT01261325) aimed to confirm the efficacy and safety/tolerability of BRV in adults (≥ 16-80 years) with POS.

Methods: This randomized, double-blind, placebo-controlled, multicenter study enrolled patients with uncontrolled POS despite ongoing treatment with 1-2 antiepileptic drugs.

Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures.

Purpose: To assess efficacy/tolerability of ezogabine (EZG)/retigabine (RTG) in combination with specified monotherapy antiepileptic drug (AED) treatments in adults with uncontrolled partial-onset seizures using a flexible dosing regimen.

Methods: NCT01227902 was an open-label, uncontrolled study of flexibly dosed EZG/RTG. Adults with partial-onset seizures must have been taking either carbamazepine/oxcarbazepine (CBZ/OXC), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA).

Dose-dependent suppression of human photoparoxysmal response with the competitive AMPA/kainate receptor antagonist BGG492: Clear PK/PD relationship.

Objective: Examine the efficacy of a competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptor antagonist, selurampanel (BGG492), in the human photostimulation model.

Methods: Patients with epilepsy and a generalized epileptiform electroencephalography response to intermittent photic stimulation (photoparoxysmal response or PPR; diagnosed ≥ 6 months prior to initial study dosing) were enrolled in a phase II, multicenter, single-blind, within-subject, placebo-controlled proof-of-concept (PoC) study. PPR was used as a biomarker to assess the efficacy and safety of BGG492 in three cohorts (cohorts I-III received BGG492 50, 100, and 15 mg, respectively).