Corpus callosotomy for intractable epilepsy: a contemporary series of operative factors and the overall complication rate.

Objective: Corpus callosotomy is an effective treatment for atonic seizures in patients with medically refractory epilepsy. A large modern series of corpus callosotomies performed via open craniotomy highlights the importance of establishing contemporary complication rates for this operation as a benchmark for comparison with newer methodologies. The authors' study, therefore, examined operative factors and complication rates for a sample of patients who underwent open microsurgical craniotomy for corpus callosotomy to determine current metrics regarding safety and effectiveness for this procedure.

Immediate Treatment of Seizure Clusters: A Conceptual Roadmap to Expedited Seizure Management.

Some patients with epilepsy continue to have seizures despite daily treatment with antiseizure medications. This includes seizure clusters (also known as acute repetitive seizures), which are an increase in seizure frequency that is different from the usual seizure pattern for that patient. In the literature, the term "rescue" is used for pharmacologic treatment for seizure clusters, but clarity regarding timing or whether a caregiver or patient should wait until a moment of life-threatening urgency before administering the medication is lacking.

Safety profile of abdominal magnetic resonance imaging (MRI) performed for renal disease surveillance in tuberous sclerosis complex patients with vagus nerve stimulation: Safety of MRI for TSC Patients with VNS.

Introduction: Individuals with tuberous sclerosis complex (TSC) often present with refractory epilepsy and may be undergoing treatment with vagus nerve stimulation (VNS) to control seizures. Surveillance magnetic resonance imaging (MRI) is necessary to monitor for the renal angiomyolipomas associated with TSC; however, MRI of the abdomen is not approved for patients withVNS therapy. We have many TSC patients with refractory epilelpsy who benefitted from VNS therapy, so we developed an MRI protocol that allows MRI of the abdomen to be performed in these patients to permit safe imaging of their kidneys.

Use of Stiripentol in Dravet Syndrome: A Guide for Clinicians.

Dravet syndrome is a developmental and epileptic encephalopathy characterized by frequent, prolonged convulsive seizures and status epilepticus. Symptoms usually appear in the first year of life, and in addition to ongoing severe and intractable epilepsy, children with Dravet syndrome experience neurodevelopmental, behavioral, and motor impairments, along with high rates of mortality, especially in the first 12 years of life. Prompt diagnosis and initiation of treatment with broad-spectrum antiseizure medications are recommended to reduce seizure frequency and status epilepticus, and to potentially minimize the comorbidities associated with the epileptic encephalopathy.

Expert opinion on use of vagus nerve stimulation therapy in the management of pediatric epilepsy: A Delphi consensus study.

Purpose: To provide consensus-based recommendations for use of vagus nerve stimulation (VNS) therapy in the management of pediatric epilepsy.

Methods: Delphi methodology with two rounds of online survey was used to build consensus. A steering committee developed 43 statements related to pediatric epilepsy and the use of VNS therapy, which were evaluated by a panel of 12 neurologists/neurosurgeons with expertise in pediatric epilepsy, who graded their agreement with each statement on a scale of 1 ("I do not agree at all") to 5 ("I strongly agree").

Return to full baseline functionality after repeated intermittent use of midazolam nasal spray in patients with seizure clusters: Post hoc analysis of an open-label extension trial.

Objective: To characterize the time to return to full baseline functionality (RTFBF) in seizure cluster episodes (SCEs) treated with one or two midazolam nasal spray (MDZ-NS/Nayzilam®) doses over the course of repeated intermittent use in patients with seizure clusters (SCs).

Methods: Post hoc analysis of an open-label extension trial in patients (≥12 years) with SCs (ARTEMIS-2/P261-402: NCT01529034, 2011-004109-25). Caregivers administered MDZ-NS 5 mg when patients experienced an SC; a second 5-mg dose could be given if seizures did not terminate within 10 min or recurred within 10 min-6 h.

Role of cholesterol in modulating brain hyperexcitability.

Cholesterol is a critical molecule in the central nervous system, and imbalances in the synthesis and metabolism of brain cholesterol can result in a range of pathologies, including those related to hyperexcitability. The impact of cholesterol on disorders of epilepsy and developmental and epileptic encephalopathies is an area of growing interest. Cholesterol cannot cross the blood-brain barrier, and thus the brain synthesizes and metabolizes its own pool of cholesterol.

Impact of Age and Concurrent Antiseizure Medication Use on Lacosamide Dose to Concentration Ratio and Dosing in Pediatric Patients.

Objective: To evaluate age, adjunctive antiseizure medication (ASM), and specific ASMs on lacosamide (LCM) weight normalized dose-to-concentration ratio (DCR) and US Food and Drug Administration (FDA) dosing guidelines in pediatric patients.

Methods: Patients 1 mo to ≤18 years with a LCM serum concentration between October 2009 and June 2017 were considered. Demographics, LCM DCR, and adjunctive ASM were recorded.

Dysphagia in Epilepsy Patients: The Silent Enemy.

Purpose Of Review: Dysphagia, or difficulty swallowing, affects several individuals globally and can contribute to a reduced quality of life and partial medication adherence, especially in patients with epilepsy. There is also a lack of awareness and understanding of dysphagia among both health care providers and patients. This review examines the interplay between dysphagia and epilepsy treatment and the potential for optimizing diagnosis and intervention.

A Retrospective Review of Reclassification of Variants of Uncertain Significance in a Pediatric Epilepsy Cohort Undergoing Genetic Panel Testing.

Background: The interpretation and communication of variant of uncertain significance (VUS) genetic results often present a challenge in clinical practice. VUSs can be reclassified over time into benign/likely benign (B/LB) or pathogenic/likely pathogenic (P/LP) based on the availability of updated data. We evaluate the frequency of VUS reclassification in our tertiary care epilepsy cohort undergoing epilepsy genetic panel (EGP) testing.

Prospective multicenter study of continuous tonic-clonic seizure monitoring on Apple Watch in epilepsy monitoring units and ambulatory environments.

Objective: Evaluate the performance of a custom application developed for tonic-clonic seizure (TCS) monitoring on a consumer-wearable (Apple Watch) device.

Methods: Participants with a history of convulsive epileptic seizures were recruited for either Epilepsy Monitoring Unit (EMU) or ambulatory (AMB) monitoring; participants without epilepsy (normal controls [NC]) were also enrolled in the AMB group. Both EMU and AMB participants wore an Apple Watch with a research app that continuously recorded accelerometer and photoplethysmography (PPG) signals, and ran a fixed-and-frozen tonic-clonic seizure detection algorithm during the testing period.

Clinical Experience With Lacosamide as an Adjunct Treatment for Neonatal Seizures: A Retrospective Single-Center Study.

Background: Lacosamide (LCM) is a third-generation antiseizure medication (ASM) currently approved for the treatment of focal seizures in children aged greater than one month. There are limited data on its efficacy in the neonatal age group. We describe our experience with LCM as an adjunct ASM for the treatment of neonatal seizures.

Diazepam nasal spray administration is effective to control seizure clusters irrespective of time of day.

Introduction: Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.

Concordance between Wada, Transcranial Magnetic Stimulation, and Magnetoencephalography for Determining Hemispheric Dominance for Language: A Retrospective Study.

Determination of language hemispheric dominance (HD) in patients undergoing evaluation for epilepsy surgery has traditionally relied on the sodium amobarbital (Wada) test. The emergence of non-invasive methods for determining language laterality has increasingly shown to be a viable alternative. In this study, we assessed the efficacy of transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), compared to the Wada test, in determining language HD in a sample of 12 patients.

Phase IV PROVE study: Perampanel in real-world clinical care of pediatric patients with epilepsy.

Introduction: The non-interventional Phase IV PROVE study (NCT03208660) assessed retention, efficacy, safety and tolerability, and perampanel dosing in patients with epilepsy during routine clinical care. This analysis evaluated final data from patients aged <4 years and 4-<12 years.

Methods: Data were obtained retrospectively from medical/pharmacy records of patients in the United States initiating perampanel after January 1, 2014, according to treating clinician recommendations.

Lacosamide extended-release capsules are bioequivalent to lacosamide immediate-release tablets: Pharmacokinetic observations and simulations.

Objectives: Assess the bioequivalence of lacosamide extended-release (XR) capsules and immediate-release (IR) tablets and answer real-world clinical questions regarding the use of lacosamide XR.

Methods: An open-label, randomized, two-treatment, two-sequence, oral comparative bioavailability study was conducted to assess the bioequivalence of two lacosamide formulations. Participants were randomized 1:1 to receive lacosamide XR capsules (400 mg once-daily) or IR tablets (200 mg twice-daily) in 1 of 2 sequences over 7-day periods.

Safety and effectiveness of diazepam nasal spray in male and female patients: Post hoc analysis of data from a phase 3 safety study.

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]).

Pitfalls of using video-EEG for a trial endpoint in children aged <4 years with focal seizures.

Objective: Double-blind, randomized, and placebo-controlled trial SP0967 (NCT02477839/2013-000717-20) did not demonstrate superior efficacy of lacosamide versus placebo in patients aged ≥1 month to <4 years with uncontrolled focal seizures, per ≤72 h video-electroencephalogram (video-EEG)-based primary endpoints (reduction in average daily frequency of focal seizures at end-of-maintenance [EOM] versus end-of-baseline [EOB], patients with ≥50% response). This was unexpected because randomized controlled trial SP0969 (NCT01921205) showed efficacy of lacosamide in patients aged ≥4 to <17 years with uncontrolled focal seizures. SP0969's primary endpoint was based on seizure diary instead of video-EEG, an issue with the latter being inter-reader variability.

Analyses of patients who self-administered diazepam nasal spray for acute treatment of seizure clusters.

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase 3 safety study.

Comparing the efficacy of awake and sedated MEG to TMS in mapping hand sensorimotor cortex in a clinical cohort.

Non-invasive methods such as Transcranial Magnetic Stimulation (TMS) and magnetoencephalography (MEG) aid in the pre-surgical evaluation of patients with epilepsy or brain tumor to identify sensorimotor cortices. MEG requires sedation in children or patients with developmental delay. However, TMS can be applied to awake patients of all ages with any cognitive abilities.

Zonisamide: A Comprehensive, Updated Review for the Clinician.

Purpose Of Review: Zonisamide (ZNS) was first approved in the United States in 2000 for the adjunctive treatment of patients aged 16 years or older with partial (focal) seizures. Although ZNS has been proven to treat multiple seizure types, it has been largely underutilized in US clinical practice.

Recent Findings: Published literature demonstrated that antiseizure medications (ASMs) acting on Na and Ca channels may add beneficial effects in many seizure types by reducing seizure frequency and leading to overall improvements.

Practical Questions About Rescue Medications for Acute Treatment of Seizure Clusters in Children and Adolescents with Epilepsy in the USA: Expanding Treatment Options to Address Unmet Needs.

Epilepsy is a common pediatric neurological condition, affecting approximately 470,000 children in the USA and having a prevalence of 0.9% in the global population of approximately 2.6 billion children.

Effectiveness, safety and tolerability of perampanel by age group when used to treat people with focal and generalized epilepsy in clinical practice: The PERMIT Extension study.

Objective: To assess the effectiveness and safety/tolerability of perampanel (PER) in people with epilepsy (PWE) treated in everyday clinical practice for focal and generalized seizures, both in the total cohort and by age group.

Methods: The PERMIT Extension study was a pooled analysis of data from PWE included in two large previous clinical practice studies (PERMIT and PROVE). Retention was assessed over 12 months.