Psychosocial outcomes of repeated treatment of seizure clusters with midazolam nasal spray: Results of a phase 3, open-label extension trial.

Objective: To evaluate treatment satisfaction, level of anxiety, confidence about traveling with midazolam nasal spray (MDZ-NS), and health-related quality of life in patients with seizure clusters and their caregivers after repeated, intermittent use of MDZ-NS in the outpatient setting.

Methods: We analyzed the psychosocial outcome data from a phase 3, open-label extension trial (ARTEMIS-2; P261-402; NCT01529034) in patients 12 years of age and older with seizure clusters on a stable regimen of antiseizure medications. Caregivers administered MDZ-NS 5 mg when patients experienced a seizure cluster.

Long-term safety and efficacy of brivaracetam in adults with focal seizures: Results from an open-label, multinational, follow-up trial.

Background: This long-term follow-up (LTFU) trial was conducted to evaluate the long-term safety and tolerability of brivaracetam (BRV) at individualized doses (maximum of 200 mg/day) in patients with focal seizures. The secondary objective was to evaluate the efficacy of BRV over time.

Methods: Two Phase III, randomized, double-blind, historical-controlled conversion-to-monotherapy trials (N01276: NCT00698581; N01306: NCT00699283) were conducted in patients aged ≥16 years with uncontrolled focal seizures.

Brivaracetam-induced elevation of carbamazepine epoxide levels: A post-hoc analysis from the clinical development program.

To assess the association, if any, between brivaracetam (BRV)-induced elevated carbamazepine-10,11-epoxide (CBZ-E) and toxicity and efficacy in patients with epilepsy. Data were pooled from three double-blind, placebo-controlled, Phase III studies of adjunctive BRV in adults with uncontrolled focal seizures (N01252/NCT00490035, N01253/NCT00464269, N01358/NCT01261325). Treatment-emergent adverse events (TEAEs) of interest (ataxia, diplopia, dizziness, nystagmus, somnolence, accidental overdose or poisoning, and toxicity), discontinuations due to TEAEs, and serious TEAEs (SAEs) were assessed in subgroups who did/did not receive carbamazepine (CBZ) at study entry (CBZ+ and CBZ-).

Conversion to brivaracetam monotherapy for the treatment of patients with focal seizures: Two double-blind, randomized, multicenter, historical control, Phase III studies.

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) approved for monotherapy (in the USA) and adjunctive treatment of focal (partial-onset) seizures in adults, at a dose range of 50-200 mg/day taken in two equal doses, with a recommended starting dose of 100 mg/day. Two Phase III, randomized, double-blind, multicenter, historical-controlled, conversion-to-monotherapy studies (N01276, NCT00698581; N01306, NCT00699283) were conducted to evaluate the efficacy, safety, and tolerability of conversion to BRV 50 mg/day monotherapy in adults with uncontrolled focal seizures. Patients aged 16-75 years, with 2-40 focal seizures per 4 weeks during an 8-week baseline, and on stable doses of 1-2 AEDs were enrolled.

An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam.

We evaluated nonpsychotic behavioral adverse events (BAEs) in patients receiving levetiracetam (LEV) who switched to brivaracetam (BRV). Patients ≥16 years of age, receiving 2-3 antiepileptic drugs (AEDs), including LEV 1-3g/day, and experiencing BAEs within 16 weeks of LEV treatment initiation, enrolled in an open-label Phase 3b study (NCT01653262) comprising a ≤1-week screening period, an immediate switch from LEV to BRV 200mg/day (without titration), and a 12-week treatment period. The percentages of patients with investigator-assessed clinically meaningful reduction in BAEs, shift in maximum BAE intensity, and change in health-related quality of life (HRQoL) (Patient-Weighted Quality of Life in Epilepsy Inventory-Form 31 [QOLIE-31-P]) were assessed.

Efficacy of once-daily extended-release topiramate (USL255): a subgroup analysis based on the level of treatment resistance.

Results from a previously conducted global phase III study (PREVAIL; NCT01142193) demonstrate the safety and efficacy of once-daily USL255, Qudexy™ XR (topiramate) extended-release capsules, as adjunctive treatment of drug-resistant partial-onset seizures (POSs). In this study, we report a post hoc analysis of PREVAIL data according to patient level of treatment resistance (based upon the number of concomitant antiepileptic drugs [AEDs] and lifetime AEDs) at baseline, with patients defined as either having "highly" drug-resistant seizures (≥ 2 concurrent AEDs and ≥ 4 lifetime AEDs) or having "less" drug-resistant seizures (1 concurrent AED or <4 lifetime AEDs) at baseline. For each subgroup, median percent reduction in POS frequency (primary endpoint), responder rate, Clinical Global Impression of Change (CGI-C), and Quality of Life in Epilepsy--Problems (QOLIE-31-P) survey were assessed.

Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study.

Objective: To evaluate the efficacy and safety of USL255, Qudexy(™) XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs.

Methods: In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥ 50% reduction in seizure frequency).

Pregabalin monotherapy in patients with partial-onset seizures: a historical-controlled trial.

Objective: To assess pregabalin monotherapy for partial-onset seizures using a historical-controlled conversion-to-monotherapy design.

Methods: Adults with inadequately controlled partial-onset seizures while receiving 1 or 2 antiepileptic drugs during an 8-week prospective baseline were randomized to double-blind monotherapy with pregabalin 600 or 150 mg/d (4:1) for 20 weeks (8-week conversion and 12-week monotherapy period). The primary endpoint was the seizure-related exit rate for pregabalin 600 mg/d, based on discontinuations due to predefined criteria.

Objective evaluation of personality and psychopathology in temporal lobe versus extratemporal lobe epilepsy.

Previous research has been equivocal on personality trait and psychopathology differences between temporal lobe and other types of epilepsy, as well as between patients with right and left temporal lobe seizure foci. In this study, personality differences between patients with right temporal (n=23), left temporal (n=21), and extratemporal (n=24) epilepsy were investigated using the NEO Personality Inventory-Revised (NEO-PI-R). No statistically significant differences were found on any of the NEO-PI-R domains or facet trait scales.

Effects of lamotrigine compared with levetiracetam on anger, hostility, and total mood in patients with partial epilepsy.

Purpose: To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures.

Methods: This randomized, double-blind, parallel-group study in adults with partial seizures included an 8-week escalation phase, during which adjunctive lamotrigine (n = 132) or adjunctive levetiracetam (n = 136) was titrated to a target dose, and a 12-week, double-blind maintenance phase, during which dosages of study medication and concomitant antiepileptic drugs were maintained. The primary endpoint was change from baseline to the end of the maintenance phase (week 20) in the Anger-Hostility subscale score of the Profile of Mood States (POMS).

Effects of lamotrigine on mood in older adults with epilepsy and co-morbid depressive symptoms: an open-label, multicentre, prospective study.

Background: Both epilepsy and depressive symptoms are more prevalent in older individuals than in any other age group. Furthermore, depressive symptoms are among the most common interictal psychiatric co-morbid disorders in people with epilepsy. For these reasons, pharmacological treatment of epilepsy that might also confer antidepressant effects may be particularly beneficial in older patients.

Continuous spikes and waves during slow sleep in an adult.

Continuous spikes and waves during slow wave sleep (CSWS) is rare and is considered to be an age-related epileptic syndrome occurring only in children. We report the case of a 21-year-old patient diagnosed with this syndrome. The patient had a history of seizures since the age of 3 and was admitted for continuous video/EEG monitoring to evaluate seizure exacerbation and unprovoked outbursts of anger.

Conversion to lamotrigine monotherapy from valproate monotherapy in older adolescent patients with epilepsy.

Background: Pharmacokinetic interactions can make necessary anti-epileptic medication (AED) changes hazardous for children with epilepsy. We report the utility of a dosing algorithm designed to maintain stable trough lamotrigine (LTG) concentrations during conversion from valproate (VPA) to LTG monotherapy in adolescents aged 16-20 years.

Methods: Patients were enrolled into the study if they required a change in their AED regimen due to lack of efficacy or intolerable side effects.

Effectiveness of diazepam rectal gel in adults with acute repetitive seizures and prolonged seizures: a single-center experience.

Many adults with epilepsy have breakthrough seizures despite treatment with antiepileptic drugs (AEDs), requiring them to have a rescue medication as part of a comprehensive treatment plan. We evaluated the effectiveness and tolerability of rectal diazepam in the treatment of breakthrough seizures in adult patients with epilepsy. We identified 50 such patients who had used diazepam rectal gel for clusters of seizures defined as acute repetitive seizures, prolonged seizures, or both, in the previous 18 months.

Epilepsy and the impact of an epileptology clinic for patients with mental retardation and associated disabilities in an institutional setting.

Purpose: Epilepsy is a common problem in institutionalized patients with multiple handicaps. Limited data exist on the characteristics of epilepsy in this patient population and the impact of systematic evaluation by an epilepsy service.

Methods: We evaluated 138 patients with epilepsy, institutionalized at a facility that cares for 324 patients with multiple handicaps.

Lamotrigine in patients with epilepsy and comorbid depressive symptoms.

Purpose: This open-label study evaluated the antidepressant qualities of lamotrigine (LTG) in people with epilepsy.

Methods: Eligible patients exhibited low to moderate depressive symptoms and required a change in antiepileptic drug (AED) therapy, but were excluded if they had a major depressive disorder (MDD). Lamotrigine was added onto a stable AED regimen, and self-report instruments were administered to evaluate changes in mood states.

Performance of patients with epilepsy or psychogenic non-epileptic seizures on four measures of effort.

Exaggeration of cognitive symptoms or poor effort on cognitive testing has been addressed primarily in the traumatic brain injury literature. The present investigation aims to extend the evaluation of effort to the epilepsy monitoring setting, where base rates of failure on effort testing remain unknown for patients with intractable epilepsy (ES), psychogenic nonepileptic seizures (PNES), or both conditions (ES+PNES). In addition, this investigation explores how well four measures of effort (DMT, LMT, TOMM, PDRT) distinguish between these diagnostic groups.

Relationship of indicators of neuropathology, psychopathology, and effort to neuropsychological results in patients with epilepsy or psychogenic non-epileptic seizures.

Previous research suggests epilepsy and psychogenic non-epileptic seizure (PNES) patients do not show consistent group differences on neuropsychological measures. However, both groups of patients show decreased neuropsychological performance when compared to a normal population (Cragar, Berry, Fakhoury, Cibula, & Schmitt, 2002). Swanson, Springer, Benbadis, and Morris (2000) have suggested epilepsy patients show decreased neurocognitive functioning due to neuropathology whereas PNES patients show decreased neurocognitive functioning due to psychopathology.

Stability of salivary concentrations of the newer antiepileptic drugs in the postal system.

Saliva antiepileptic drug (AED) concentrations strongly correlate with serum concentrations. Saliva collection is painless and noninvasive, and untrained personnel can easily be taught the collection process. Remote patients could mail saliva samples to a laboratory for monitoring, and samples could be obtained in the immediate postictal state to provide a "real-time" concentration.

Cluster analysis of normal personality traits in patients with psychogenic nonepileptic seizures.

The literature on patients with psychogenic nonepileptic seizures (PNES) suggests that they are a heterogeneous population. This study addresses this heterogeneity by describing subtypes of PNES based on a cluster analysis of normal personality traits in patients with PNES. In addition, the identified PNES subtypes are further described on dimensions of psychopathology as measured by the Minnesota Multiphasic Personality Inventory, Second Edition (MMPI-2), and cognition.

Efficacy and tolerability of conversion to monotherapy with lamotrigine compared with valproate and carbamazepine in patients with epilepsy.

Objective: This randomized, open-label study was designed to compare the efficacy and tolerability of lamotrigine monotherapy with those of valproate and carbamazepine monotherapy in patients with epilepsy whose seizures were uncontrolled on their prestudy antiepileptic drug monotherapy.

Methods: Patients meeting eligibility criteria were randomized 2:1 to lamotrigine:carbamazepine or lamotrigine:valproate. The treatment phase was divided into a 4-week dose-escalation phase (Weeks 1-4), during which lamotrigine, carbamazepine, or valproate was added to patient's prestudy monotherapy; an 8-week add-on phase (Weeks 5-12), during which patients were stabilized on both the study medication and their prestudy antiepileptic therapy; an 8-week withdrawal phase (Weeks 13-20), during which prestudy antiepileptic therapy could be withdrawn if clinically appropriate; and an 8-week monotherapy phase (Weeks 21-28), during which patients could be treated with study medication as monotherapy.

Feasibility and limitations of oxcarbazepine monitoring using salivary monohydroxycarbamazepine (MHD).

The purpose of this study is to determine the feasibility of using 10-hydroxy-10,11-dihydrocarbazepine (MHD) concentration in saliva as an alternative to serum for the therapeutic monitoring of oxcarbazepine (OXC) treatment. Investigators identified subjects seen in neurology clinics at the University of Kentucky Chandler Medical Center. Patients were eligible if they agreed to participate in this study, were taking oxcarbazepine, and if a serum MHD concentration had been ordered by their physician.

Topiramate and status epilepticus: report of three cases.

Objective: The goal of this study was to report the effectiveness of topiramate in treating status epilepticus.

Methods: Three patients with status epilepticus were treated with topiramate 500 mg twice daily for 2-5 days, with the dose gradually tapered thereafter to 200 mg twice daily. The patients' clinical status and EEG recordings were followed.

Correlation of lamotrigine concentrations between serum and saliva.

Study Objective: To compare the relationship between serum and salivary concentrations of lamotrigine in pediatric and adult epilepsy populations.

Design: Paired-sample pharmacokinetic study.

Setting: University neurology clinic.

Bilateral abducens nerve palsy from mild trauma with force applied at an oblique angle: a case report and review of the literature.

Traumatic bilateral abducens nerve palsy is rare. Bilateral palsy due to a force applied at an angle is even more unusual. We report a case of bilateral traumatic abducens nerve palsy without fracture after striking the right side of the face in a fall.